| 1. |
- Andersson, Per-Erik, et al.
(författare)
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Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow
- 1998
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Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 7:2, s. 118-126
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). Conclusion: Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.
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| 2. |
- Carlstedt, F., et al.
(författare)
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Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department
- 1997
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 27:12, s. 977-981
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Tidskriftsartikel (refereegranskat)abstract
- Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.
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| 3. |
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| 4. |
- Edholm, David, et al.
(författare)
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Preoperative 4-week low-calorie diet reduces liver volume and intrahepatic fat, and facilitates laparoscopic gastric bypass in morbidly obese
- 2011
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 21:3, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to explore changes in liver volume and intrahepatic fat in morbidly obese patients during 4 weeks of low-calorie diet (LCD) before surgery and to investigate if these changes would facilitate the following laparoscopic gastric bypass.METHODS: Fifteen female patients (121.3 kg, BMI 42.9) were treated preoperatively in an open study with LCD (800-1,100 kcal/day) during 4 weeks. Liver volume and fat content were assessed by magnetic resonance imaging and spectroscopy before and after the LCD treatment.RESULTS: Liver appearance and the complexity of the surgery were scored at the operation. Eighteen control patients (114.4 kg, BMI 40.8), without LCD were scored similarly. Average weight loss in the LCD group was 7.5 kg, giving a mean weight of 113.9 kg at surgery. Liver volume decreased by 12% (p < 0.001) and intrahepatic fat by 40% (p < 0.001). According to the preoperative scoring, the size of the left liver lobe, sharpness of the liver edge, and exposure of the hiatal region were improved in the LCD group compared to the controls (all p < 0.05).CONCLUSIONS: The overall complexity of the surgery was perceived lower in the LCD group (p < 0.05), due to improved exposure and reduced psychological stress (both p < 0.05). Four weeks of preoperative LCD resulted in a significant decrease in liver volume and intrahepatic fat content, and facilitated the subsequent laparoscopic gastric bypass as scored by the surgeon
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| 5. |
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| 6. |
- Fugmann, Andreas, et al.
(författare)
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The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose uptake in the human forearm
- 1998
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 35:4, s. 203-206
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed to be of major importance for insulin-mediated glucose uptake. The aim of this study was to investigate the relative importance of blood flow and glucose extraction as determinants of insulin-mediated glucose uptake in the human forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in nine healthy subjects. FBF was measured by venous occlusion plethysmography. Forearm glucose uptake increased sevenfold during the hyperinsulinaemia (P<0.001). Forearm glucose extraction showed a minor increase during the first 10 min of hyperinsulinaemia, but the most marked increase took place between 10 and 20 min (+170%). Thereafter, only a minor further increase was seen. During the first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased steadily to a plateau reached after 60 min (+50%, P<0.001). A close relationship between whole body glucose uptake and FBF was seen at the end of the clamp (r = 0.75, P<0.02), but at this time the relationship between whole body glucose uptake and forearm glucose extraction was not significant. The modest increase in O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF during the early phase of the clamp. In conclusion, the early course of insulin-mediated glucose uptake in the human forearm was mainly due to an increase in glucose extraction. However, with time the insulin-mediated increase in blood flow increased in importance and after 100 min of hyperinsulinaemia FBF was the major determinant of glucose uptake.
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| 7. |
- Hedberg, Jakob, et al.
(författare)
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Increased plasma magnesium concentrations 3 years after biliopancreatic diversion with duodenal switch
- 2012
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 22:11, s. 1708-1713
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Tidskriftsartikel (refereegranskat)abstract
- Background Biliopancreatic diversion with duodenal switch, BPD-DS, is a surgical procedure for treatment of super obese patients. It renders very good weight results and it strongly reduces the incidence of type 2 diabetes. One important mechanism of weight reduction after BPD-DS is malabsorption. Hypomagnesemia is an established cardiovascular risk factor. While it is wellknown that magnesium levels decline after jejuno-ileal bypass and increase after gastric bypass surgery, information on how magnesium status is affected by BPDDS is scant. The aim of the present study was to evaluate plasma magnesium concentrations (P-Mg) after BPD-DS. Methods Thirty-one patients, all Caucasians (9 diabetics, 12 men, age 38±8 years, weight 159±22 kg, body mass index (BMI) 53.9±5.2 kg/m 2) underwent BPD-DS. We evaluated weight, glycated hemoglobin levels (HbA1c) and P-Mg preoperatively as well as at 1 and 3 years after surgery. All subjects were treated with vitamin and mineral substitution after surgery, including 100 mg of magnesium salt. P-Mg was analyzed with respect to changes over time, correlation to BMI and HbA1c levels before and 3 years after surgery. Results The plasma magnesium concentrations increased by 15 % from 0.77±0.07 to 0.88±0.09 mmol/l over 3 years (p <0.001). The weight loss was 71±25 kg. No patient had diabetes at follow-up. No correlations between P-Mg and BMI or HbA1c were seen. Conclusions Although exerting much of its weightreducing effect by a malabsorptive mechanism, BPD-DS yields a rise in P-Mg 3 years postoperatively, possibly contributing to the improved metabolic state after this operation.
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| 8. |
- Hänni, Arvo, et al.
(författare)
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Increased circulating magnesium concentrations after Roux-en-Y gastric bypass surgery in patients with type 2 diabetes
- 2018
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier. - 1550-7289 .- 1878-7533. ; 14:5, s. 576-582
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low circulating magnesium concentrations predict cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D). Epidemiologic and clinical studies have indicated lower extra- and intracellular magnesium concentrations in patients with diabetes.Objective: We aimed to describe alterations, if any, in circulating magnesium concentrations after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in patients with obesity and T2D.Setting: Outpatient clinic of obesity and central hospital.Methods: Retrospective analysis of 1-year outcome of plasma magnesium (p-Mg) and glucometabolic status in all consecutive patients who underwent primary LRYGBP and who completed the follow-up visits, including biochemical test panels 6 and 12 months after surgery.Results: LRYGBP and complete follow-up visits were performed in 51 patients with T2D and 86 patients without T2D. All patients were given similar dietary advice and multivitamin and mineral supplementation after surgery. Before RYGB, the patients with T2D showed lower p-Mg compared with patients without T2D (.79 ± .06 mM and .82 ± .05 mM, respectively, P<.01). P-Mg was inversely correlated to fasting blood glucose and glycosylated hemoglobin levels. After surgery, mean p-Mg increased by 5.2% in the group with T2D compared with 1.4% in the patients without T2D (P<.01), ending at an equal level of .83 mM. The alterations in p-Mg were inversely related to the changes in fasting glucose and glycosylated hemoglobin concentrations.Conclusion: The lowered p-Mg associated with impaired glucometabolic status in patients with T2D was increased after LRYGBP, reaching similar concentrations as in patients without T2D.
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| 9. |
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| 10. |
- Hänni, Arvo
(författare)
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Magnesium and the Insulin Resistance Syndrome
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin resistance, defined as a state of reduced insulin-mediated glucose uptake in peripheral tissues, and disorders such as obesity, hypertension, and dyslipidemia, have been found to be associated in the conglomerate of the insulin resistance syndrome. Some antihypertensive drugs have been shown to decrease insulin sensitivity further. In the studies described in this thesis relations between the magnesium status and some aspects of the insulin resistance syndrome were investigated. In a cross-sectional study serum Mg was found to be directly related to insulin sensitivity and lipoprotein lipase activity, and inversely to fasting glucose concentration. During treatment with angiotensin-converting enzyme inhibitors, ACEi, in patients with essential hypertension, an increase in serum Mg in relation to serum Ca was found to be correlated to improved insulin sensitivity and decreased serum lipid concentrations. In trials with ACEi or bendrofluazide treatment, a reduced Ca/Mg ratio in skeletal muscle was associated with the blood pressure response. A change in Mg concentration in skeletal muscle was inversely correlated to the change in serum glucose, but was not correlated to the insulin sensitivity per se. Atherogenic lipid fractions were more closely related to the plasma ionized Mg concentration than to circulating total Mg levels. Intra-arterial Mg infusion improved endothelium-dependent vasodilation, EDV, in healthy normotensive subjects. In summary, magnesium improves endothelium-dependent vasodilation and lipoprotein lipase activity, which might help to explain the inverse correlations between circulating Mg concentrations and some lipid and glucometabolic variables.The Mg content in skeletal muscle is related to blood pressure response and serum glucose levels during antihypertensive treatment with ACEi or bendrofluazide.
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| 11. |
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| 12. |
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| 13. |
- Hänni, Arvo, et al.
(författare)
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Systolic blood pressure alterations during hyperinsulinemia are related to changes in ionized calcium status
- 2001
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 14:11 Pt 1, s. 1106-1111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A correlation between changes in ionized calcium status and changes in systolic blood pressure (BP) has previously been observed during induced euglycemic hyperinsulinemia in patients with essential hypertension. The objective of this study was to evaluate associations between alterations in ion status and BP changes during euglycemic hyperinsulinemia in healthy normotensive subjects. METHODS: Ion status in plasma and BP were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 41 healthy normotensive volunteers. RESULTS: During euglycemic hyperinsulinemia plasma sodium increased by 1% (P < .0001), ionized calcium (iCa) by 5% (P < .0001), and ionized magnesium (iMg) by 4% (P < .01), whereas potassium decreased by 10% (P < .0001). The changes in plasma iCa and iMg correlated significantly to changes in systolic BP (r = -0.38, P < .02; r = -0.32, P < .05, respectively), but the correlation between changes in iMg and changes in systolic BP did not remain significant in a multiple regression model. The glucose infusion rate correlated inversely to the change in iMg (r = -0.39, P < .01). CONCLUSIONS: The group mean systolic BP was unaltered during induced euglycemic hyperinsulinemia in healthy normotensive subjects; however, a more pronounced increase in the circulating iCa concentration was associated with a greater decline in systolic BP, which is in accordance with previous observations in patients with essential hypertension. The group mean diastolic BP was decreased; however, the lowered diastolic BP was not correlated to changes in ion status.
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| 14. |
- Hänni, Arvo, et al.
(författare)
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The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance
- 1997
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 10:2, s. 145-151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.
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| 15. |
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| 16. |
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| 17. |
- Hänni, Arvo, et al.
(författare)
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Övervikt och fetma
- 2011
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Ingår i: Läkemedelsboken. - Uppsala : Läkemedelverket. - 9789197960502 ; , s. 193-211
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Hänni, Arvo, 1952-, et al.
(författare)
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Övervikt och fetma
- 2014
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Ingår i: Läkemedelsboken. - Uppsala : Läkemedelsverket. - 9789163741500 ; , s. 201-219
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Ingelsson, Erik, et al.
(författare)
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Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:3, s. 953-957
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Skeletal muscle morphology and function are strongly associated with insulin sensitivity. OBJECTIVE: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. DESIGN, SETTINGS, AND PARTICIPANTS: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. MAIN OUTCOME MEASURES: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. RESULTS: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. CONCLUSIONS: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.
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| 20. |
- Johansson, Hans-Erik, 1960-, et al.
(författare)
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Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal
- 2010
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 20:5, s. 549-558
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Tidskriftsartikel (refereegranskat)abstract
- Hyperproinsulinemia is associated with obesity and type 2 diabetes. We explored the after-meal dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in patients treated with bileopancreatic diversion with duodenal switch (BPD-DS) surgery compared with normal-weight controls [body mass index (BMI)+/- SD, 23.2 +/- 2.4 kg/m(2)].Ten previously morbidly obese (BMI +/- SD, 53.5 +/- 3.8 kg/m(2)) patients free from diabetes who had undergone BPD-DS (BMI +/- SD, 29.0 +/- 5.2 kg/m(2)) 2 years earlier were recruited. A standardised meal (2400 kJ) was ingested, and glucose, proinsulin, insulin, free fatty acids and triglycerides (TGs) were determined during 180 min. Follow-up characteristics yearly on glucose, lipids, creatinine and uric acid over 3 years after BPD-DS are presented.Fasting glucose and insulin were lower, 0.4 mmol/L and 4.6 pmol/L, respectively, in the BPD-DS group despite higher BMI. Fasting proinsulin was similar in both groups. Postprandial area under the curve (AUC) for glucose, proinsulin and insulin did not differ between the two groups (p = 0.106-734). Postprandial changes in glucose, proinsulin and insulin were essentially similar but absolute concentrations of proinsulin and insulin were lower in the later phases in the BPD-DS group (p = 0.052-0.001). Postprandial AUC for TGs was lower in the BPD-DS group (p = 0.005). Postprandial changes in TGs were lowered in the intermediate phase (p = 0.07-0.08) and in the late phase (0.002). Follow-up data showed markedly lowered creatinine and uric acid after BPD-DS.BPD-DS surgery induces a large weight loss and lowers, close to normal, postprandial responses of glucose, proinsulin and insulin but with marked lowering of TGs.
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| 21. |
- Johansson, Hans-Erik, 1960-, et al.
(författare)
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Platelet Counts and Liver Enzymes After Gastric Bypass Surgery
- 2018
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Ingår i: Obesity Surgery. - : Springer Nature. - 0960-8923 .- 1708-0428. ; 28:6, s. 1526-1531
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with chronic inflammation, liver steatosis and increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are a biomarker reflecting inflammation and the degree of fibrosis in NAFLD. We investigated alterations in PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric bypass (RYGBP). One hundred twenty-four morbidly obese non-diabetic patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP. Body mass index (BMI) was reduced from 43.5 kg/m(2) (baseline) to 31.1 kg/m(2) (follow-up), and p < 0.001 and weight declined from 126.2 to 89.0 kg. PCs decreased from 303 x 10(9) to 260 x 10(9)/l, p < 0.001. GGT was reduced from 0.63 to 0.38 mu kat/l, p < 0.001. ALT decreased from 0.69 to 0.59 mu kat/l, p = 0.006. CRP was lowered from 7.3 to 5.4 mg/l p < 0.001 and ferritin from 106 to 84 mu g/l p < 0.001. The alterations in PCs correlated with the changes in CRP (r = 0.38, p = 0.001), BMI (r = 0.25, p = 0.012), weight (r = 0.24, p = 0.015) and inversely correlated with ferritin (r = 21, p = 0.036). PCs, GGT and ALT (markers for NAFLD), and CRP and ferritin (markers for inflammation) decreased in morbidly obese after RYGBP. The decrease in PCs correlated with alterations in CRP, BMI, weight and ferritin. The lowering of liver enzymes may reflect a lowered liver fat content and decreased general inflammation.
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| 22. |
- Johansson, Hans-Erik, 1960-
(författare)
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The Impact of Bariatric Surgery on Obesity related Metabolic Traits with Specific Emphasis on Glucose, Insulin and Proinsulin
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hyperproinsulinemia is associated with type 2 diabetes (T2DM) and obesity and is a predictor for future coronary heart disease. This thesis examines the effect of bariatric surgery on glucometabolic status including insulin and proinsulin responses after meal. Further we explored longitudinally the effects of bariatric surgery on glucose, insulin and proinsulin secretion as well as lipids, liver enzymes and magnesium concentrations. We explored by a standardised meal test the postprandial dynamics of proinsulin and insulin and effects on glucose and lipids in patients treated with gastric bypass (RYGBP) surgery and in patients treated with bileopancreatic diversion with duodenal switch surgery (BPD-DS). Comparisons were made to morbidly obese patients and normal weight controls (NW). RYGBP surgery markedly lowers fasting and postprandial proinsulin concentrations although BMI was higher compared to NW-controls. BPD-DS surgery induces a large weight loss and normalises postprandial responses of glucose, proinsulin and insulin and markedly lowers triglycerides. We evaluated non-diabetic morbidly obese patients who underwent bariatric surgery followed-up for up to four years after surgery. Long-term follow-up showed that RYGBP surgery is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, ALT and increased HDL-C possibly via reduced hepatic insulin resistance. We also examined how magnesium status is affected by bariatric surgery as magnesium has been shown to be inversely related to glucose and to insulin resistance. The serum magnesium concentrations increased by 6% after RYGBP and 10% after BPD-DS. In summary, RYGBP and BPD-DS surgery results in marked weight loss, alterations in insulin and proinsulin dynamics, lowered fasting and postprandial proinsulin concentrations and improved glucometabolic and magnesium status.
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| 23. |
- Kiiski, Ritva, et al.
(författare)
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An inhibitor of angiotensin converting enzyme (enalapril) augments endotoxin-induced hypotension in the pig
- 1999
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734. ; 104:2, s. 163-176
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Tidskriftsartikel (refereegranskat)abstract
- Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalpril) [at a dose (0.5 mg x kg-1) that did not per se reduce mean arterial blood pressure (MAP); (n = 7)], or the corresponding volume of saline (n = 8). Another seven pigs were randomised for treatment with enalapril (0.5 mg x kg-1) + saline (n = 3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio-depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.
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| 24. |
- Lind, Lars, et al.
(författare)
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Is insulin resistance a predictor of the blood pressure response to anti-hypertensive treatment?
- 1995
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Ingår i: Journal of Human Hypertension. - 0950-9240 .- 1476-5527. ; 9:9, s. 759-763
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Tidskriftsartikel (refereegranskat)abstract
- It is a general impression that the blood pressure (BP) response during monotherapy in hypertensive subjects is highly variable. As decreased insulin sensitivity is a frequent finding in hypertensive patients, the following study was performed to evaluate if the degree of insulin sensitivity could predict the BP response to different types of anti-hypertensive treatments. Insulin sensitivity was evaluated by the hyperinsulinaemic euglycaemic clamp technique before initiation of treatment with beta-adrenergic blockers (n = 181), thiazide diuretics (n = 60), ACE inhibitors (n = 73), non-dihydropyridine calcium antagonists (n = 38), dihydropyridine calcium antagonists (n = 26) or alpha-1 antagonists (n = 39) over periods of 3-6 months in hypertensive patients. The proportion of poor responders, defined as a reduction in the diastolic blood pressure (DBP) of < 3 mm Hg ranged between 8% and 30% in the different groups despite similar pretreatment DBPs (100-102 mm Hg). A decreased pretreatment insulin sensitivity was related to a poor DBP treatment response in the thiazide-treated group only (r = -0.33, P < 0.05). In this group also obesity, as evaluated by body mass index (BMI), was associated with a poor BP response (r = 0.28, P < 0.05), while obesity was a predictor of a favourable reduction in DBP in the group treated with non-dihydropyridine calcium antagonists (r = -0.34, P < 0.05). These associations were still significant when pretreatment DBP was taken into account in multiple regression analysis. Neither age nor sex were found to be significant predictors of BP response in any of the treatment groups.(
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| 25. |
- Lind, Lars, et al.
(författare)
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Left ventricular hypertrophy in hypertension is associated with the insulin resistance metabolic syndrome
- 1995
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 13:4, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether left ventricular hypertrophy is associated with the insulin resistance syndrome. METHODS: Fifty patients with untreated hypertension were evaluated by recording office blood pressure during regular antihypertensive treatment and 24-h ambulatory blood pressure and office blood pressure after 4-6 weeks on placebo, echocardiography with M-mode measurements of left ventricular wall thickness and pulsed-wave Doppler measurements of mitral flow in diastole and the hyperinsulinaemic euglycaemic clamp, for determination of insulin sensitivity. RESULTS: The left ventricular wall thickness was found to be significantly related to blood pressure [r = 0.44, P < 0.004 for 24-h ambulatory systolic blood pressure (SBP)], fasting insulin level (r = 0.32, P < 0.03) and haematocrit level (r = 0.37, P < 0.009) and inversely related to insulin sensitivity (r = -0.59, P < 0.0001). Multiple regression analysis with these relationships together with confounding factors age, sex, body mass index and waist: hip ratio as independent variables showed insulin sensitivity to be the only significant variable, explaining 43% of the variation in left ventricular wall thickness, whereas 24-h ambulatory SBP explained a further 7%. Left ventricular diastolic filling, as evaluated by the mitral Doppler early: atrial ratio, was significantly correlated with insulin sensitivity (r = 0.42, P < 0.003) and inversely related to blood pressure (r = -0.41, P < 0.02 for 24-h ambulatory SBP), left ventricular wall thickness (r = -0.34, P < 0.02) and serum fibrinogen level (r = -0.63, P < 0.0001). However, multiple regression analysis showed that insulin sensitivity was more closely related to diastolic filling than to blood pressure or left ventricular wall thickness. CONCLUSION: The present study showed left ventricular wall thickness to be closely associated with insulin resistance. Because diastolic dysfunction of the left ventricle was also related to a decreased insulin sensitivity, these findings suggest that left ventricular hypertrophy and diastolic dysfunction are associated with the insulin resistance metabolic syndrome.
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| 26. |
- Lind, Lars, et al.
(författare)
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The haemodynamic response to hyperinsulinaemia in hypertensive subjects
- 1999
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Ingår i: Journal of Human Hypertension. - 0950-9240 .- 1476-5527. ; 13:1, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- In order to study if the vasodilatory action of insulin is impaired in essential hypertension, 24 untreated patients were challenged with a 2 h euglycaemic hyperinsulinaemic clamp (56 E/m2). Cardiac index (CI) was measured by thoracic impedance cardiography and leg blood flow (LBF) by Doppler ultrasound. During the clamp procedure a significant decline in blood pressure was seen (3.0-5.6% over 120 min, P < 0.001). However, no significant effects on ejection fraction (+6 +/- 8 s.d.%), CI (-1 +/- 2%), heart rate (+2 +/- 1%) or total peripheral resistance (TPRI, -0.5 +/- 2%) were found. LBF increased by 22 +/- 35% (P < 0.005). These haemodynamic effects of insulin were not related to age, sex, body mass index, blood pressure or the insulin-mediated glucose uptake during the clamp. In conclusion, insulin increased LBF, but no changes in CI and TPRI were seen in the hypertensive patients. Furthermore, no association between the ability of insulin to induce vasodilatation and to promote glucose uptake was seen.
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| 27. |
- Lind, Lars, et al.
(författare)
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Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men
- 1995
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 8:9, s. 894-901
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Tidskriftsartikel (refereegranskat)abstract
- A previous study has shown that serum levels of the active vitamin D metabolite 1,25-(OH)2-vitamin D were inversely related to blood pressure levels while the prohormone 25-OH-vitamin D was found to be related to insulin metabolism. Also other clinical and experimental data support the view that vitamin D metabolism is involved in blood pressure regulation and other metabolic processes. The present study was conducted in order to see if the above mentioned relationships between the vitamin D endocrine system and blood pressure, as well as other cardiovascular risk factors, could be found in a cross-section population-based study. Serum levels of 1,25-(OH)2-vitamin D, 25-OH-vitamin D, and blood pressure were therefore measured in 34 middle-aged men and metabolic cardiovascular risk factors were evaluated by means of intravenous glucose and fat tolerance tests, euglycemic hyperinsulinemic clamp, lipoprotein measurements, and lipoprotein lipase activity determinations. Serum levels of 1,25-(OH)2-vitamin D were found to be inversely correlated to the blood pressure (r = -0.42, P < .02), VLDL triglycerides (r = -0.47, P < .005), and to triglyceride removal at the intravenous fat tolerance test (r = 0.34, P < .05), while serum levels of 25-OH-vitamin D were correlated to fasting insulin (r = -0.35, P < .05), insulin sensitivity during clamp (r = 0.54, P < .001), and lipoprotein lipase activity both in adiposal tissue (r = 0.48, P < .005) and skeletal muscle (r = 0.38, P < .03).(
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| 28. |
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| 29. |
- Lithell, Hans, et al.
(författare)
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Epidemiological and clinical studies on insulin resistance and diabetes
- 2000
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734. ; 105:2, s. 135-150
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- In Uppsala, extensive epidemiological and clinical studies on insulin resistance and diabetes have been ongoing for the past 30 years. A prospective cohort study of men born 1920-24, living in Uppsala County, was initiated during 1969-74 (the Uppsala Longitudinal Study of Adult Men, ULSAM). Risk factors for cardiovascular disease were examined in 2,322 men, and re-examinations have been performed every 10 years. At the first follow-up, when the men were 60 years old, insulin resistance was found to be a risk factor for development of hypertension and diabetes. In addition, treatment with antihypertensive medication was an independent risk factor for development of diabetes. These findings resulted in a series of clinical studies on metabolic effects of antihypertensive agents. At the second follow-up, when the men were 70 years old, the development of hypertension and diabetes was once again in focus, but at this time, cross-sectional and prospective studies of other cardiovascular determinants, such as circadian blood pressure pattern, left ventricular geometry and function, muscle morphology, ion status, fibrinolysis and cognitive function, were also performed. The cohort has furthermore been linked to the Swedish census and hospital discharge and cause of death registries, it has been used for studies on relationships between birth weight and cardiovascular disease, and genetic analyses have been performed, taking advantage of the long observation time obtained in this cohort. The cohort is currently being re-examined for the third time, and will hopefully continue to provide valuable information on the epidemiology of diabetes and cardiovascular disease in the future.
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| 30. |
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| 31. |
- Nilsen, Inger, et al.
(författare)
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Comparison of Meal Pattern and Postprandial Glucose Response in Duodenal Switch and Gastric Bypass Patients
- 2019
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Ingår i: Obesity Surgery. - : SPRINGER. - 0960-8923 .- 1708-0428. ; 29:7, s. 2210-2216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bariatric surgery improves glucose homeostasis; however, side effects such as hypoglycemia can occur. We investigated the effects of meals on interstitial glucose (IG) response in biliopancreatic diversion with duodenal switch (BPD-DS) and Roux-en-Y gastric bypass (RYGBP)-operated patients at least 1 year after surgery.Methods: Thirty patients treated with BPD-DS or RYGBP were recruited at the outpatient Obesity Unit, Uppsala University Hospital. IG was measured by continuous glucose monitoring (CGM) for 3 consecutive days, and postprandial IG levels from 5 to 120 min were analyzed for 2 of these days. All intake of food and beverages was simultaneously registered in a food diary, which was processed using The Meal Pattern Questionnaire.Results: Postprandial IG levels were significantly lower in BPD-DS (n = 14) compared to RYGBP (n = 15)-treated patients, with mean concentrations of 5.0 (+/- 1.0) and 6.3 (+/- 1.8) mmol/L respectively (p < 0.001). The mean postprandial IG increment was lower in BPD-DS than in RYGBP patients, 0.2 (+/- 0.6) vs. 0.4 (+/- 1.4) mmol/L (p < 0.001). Furthermore, the postprandial IG variability was less pronounced in BPD-DS than in RYGBP patients. The mean number of daily meals did not differ between the two groups, 7.8 (+/- 2.6) in BPD-DS and 7.2 (+/- 1.7) in the RYGBP (p = 0.56).Conclusion: BPD-DS patients demonstrated lower postprandial IG concentrations, with smaller postprandial IG increments and less pronounced postprandial IG variability compared to RYGBP patients. The two groups had similar meal pattern and the postprandial IG responses is probably associated with differences in postoperative physiology.
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| 32. |
- Nilsen, Inger, Cand. Scient, 1968-, et al.
(författare)
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Glycemic variability and hypoglycemia before and after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy : A cohort study of females without diabetes
- 2024
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier. - 1550-7289 .- 1878-7533. ; 20:1, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to lower fasting glucose concentrations, but might cause higher glycemic variability (GV) and increased risk of hypoglycemia. However, it has been sparsely studied in patients without preoperative diabetes under normal living conditions.OBJECTIVES: To study 24-hour interstitial glucose (IG) concentrations, GV, the occurrence of hypoglycemia and dietary intake before and after laparoscopic RYGB and SG in females without diabetes.SETTING: Outpatient bariatric units at a community and a university hospital.METHODS: Continuous glucose monitoring and open-ended food recording over 4 days in 4 study periods: at baseline, during the preoperative low-energy diet (LED) regimen, and at 6 and 12 months postoperatively.RESULTS: Of 47 patients included at baseline, 83%, 81%, and 79% completed the remaining 3 study periods. The mean 24-hour IG concentration was similar during the preoperative LED regimen and after surgery and significantly lower compared to baseline in both surgical groups. GV was significantly increased 6 and 12 months after surgery compared to baseline. The self-reported carbohydrate intake was positively associated with GV after surgery. IG concentrations below 3.9 mmol/L were observed in 14/25 (56%) of RYGB- and 9/12 (75%) of SG-treated patients 12 months after surgery. About 70% of patients with low IG concentrations also reported hypoglycemic symptoms.CONCLUSIONS: The lower IG concentration in combination with the higher GV after surgery, might create a lower margin to hypoglycemia. This could help explain the increased occurrence of hypoglycemic episodes after RYGB and SG.
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| 33. |
- Nilsen, Inger, 1968-, et al.
(författare)
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Lower Interstitial Glucose Concentrations but Higher Glucose Variability during Low-Energy Diet Compared to Regular Diet-An Observational Study in Females with Obesity
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- This is an observational study of interstitial glucose (IG) concentrations, IG variability and dietary intake under free-living conditions in 46 females with obesity but without diabetes. We used continuous glucose monitoring, open-ended food recording and step monitoring during regular dietary intake followed by a low-energy diet (LED). Thirty-nine participants completed both study periods. The mean BMI at baseline was 43.6 & PLUSMN; 6.2 kg/m(2). Three weeks of LED resulted in a mean weight loss of 5.2% with a significant reduction in diurnal IG concentration but with greater glycemic variability observed during LED. The mean 24 h IG concentration decreased from 5.8 & PLUSMN; 0.5 mmol/L during the regular diet period to 5.4 & PLUSMN; 0.5 mmol/L (p < 0.001) during LED, while the mean amplitude of glycemic excursion increased from 1.5 & PLUSMN; 0.7 to 1.7 & PLUSMN; 0.7 mmol/L (p = 0.031). The positive incremental area under the curve at breakfast was significantly larger for LED compared to regular diet. The daily fiber intake and the glycemic index of breakfast meals were significantly associated with the glycemic variability during regular dietary intake. In conclusion, the 24 h mean IG concentration was lower but with more pronounced glycemic variability during LED compared to a regular diet.
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| 34. |
- Nilsson, Bo, et al.
(författare)
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C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors
- 2014
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Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 44:6, s. 587-596
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Tidskriftsartikel (refereegranskat)abstract
- Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals. Methods In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed. Results C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating thatthe association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4 months. Conclusion A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that theadipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity.
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| 35. |
- Olsson, Johan, et al.
(författare)
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Effect of a vegetable-oil emulsion on body composition; a 12-week study in overweight women on a meal replacement therapy after an initial weight loss : a randomized controlled trial
- 2011
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 50:4, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- The maintenance of an obtained lower weight level is often found to be difficult. The aim of this study was to determine weight maintenance after an initial weight loss by consumption of a meal replacement with a vegetable-oil emulsion associated with prolonged satiety. After a 6-week weight loss period with very low calorie diet (VLCD), subjects with > 5% body weight (BW) loss were randomized to a 12-week weight maintenance follow-up period, comparing a partial meal replacement diet containing a vegetable-oil emulsion (test) or dairy fat (control). Anthropometric data and safety variables were collected at baseline and after 4, 8 and 12 weeks. A significant weight loss was observed during the 12-week weight maintenance diet in the test and control group, respectively; 1.0 +/- A 2.1 kg (p < 0.05) versus 1.3 +/- A 2.1 kg (p < 0.05) with no significant difference between the groups. Body fat mass (BFM) decreased significantly (p < 0.05) in the test group (-1.7%) compared to the control group (-0.8%). Addition of a vegetable-oil emulsion to a meal replacement weight maintenance program after an initial weight loss using VLCD was associated with decreased BFM by 0.9% without any change in BW between the two groups.
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| 36. |
- Reneland, Richard, et al.
(författare)
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Circulating angiotensin converting enzyme levels are increased in concentric, but not eccentric, left ventricular hypertrophy in elderly men
- 1997
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 15:8, s. 885-890
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension. METHODS: Two-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity. RESULTS: The serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively, P < 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = -0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity. CONCLUSION: Levels of serum ACE activity are associated with left ventricular geometry.
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| 37. |
- Sarabi, Mahziar, et al.
(författare)
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Local vasodilatation with metacholine, but not with nitroprusside, increases forearm glucose uptake
- 1999
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Ingår i: Physiological Research. - 0862-8408 .- 1802-9973. ; 48:4, s. 291-295
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Tidskriftsartikel (refereegranskat)abstract
- Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.
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| 38. |
- Zethelius, Björn, et al.
(författare)
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Läkemedelsbehandling av fetma
- 2009. - 1
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Ingår i: Fetma - del 1. - Lund : Studentlitteratur. - 9789144018928 ; , s. 193-213
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Zethelius, Björn, et al.
(författare)
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The interaction between impaired acute insulin response and insulin resistance predict type 2 diabetes and impairment of fasting glucose : report from a 20-year follow-up in the Uppsala Longitudinal Study of Adult Men - ULSAM
- 2008
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 113:2, s. 117-130
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up. METHODS: We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated. RESULTS: In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76). CONCLUSION: The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease.
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