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| 2. |
- Fändriks, Lars, 1956, et al.
(author)
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Bariatric surgery for diabetes mellitus type 2 control in adults with BMI<35 kg/m2
- 2016
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Reports (other academic/artistic)abstract
- Background: Obesity is strongly linked to diabetes and premature mortality, mainly from cardiovascular causes. In 2013, the prevalence of obesity (BMI ≥ 30 kg/m2) in adults in Sweden was 14 %. The prevalence of diabetes mellitus in Sweden is approximately 5 % with a slow increase due to an ageing population. In 2015, 73,225 patients in VGR had a diagnosis of diabetes mellitus. The treatment of overweight and obesity in adults is based on three principles: lifestyle changes, pharmacological treatment and surgery. Today, weight reducing (bariatric) surgery can be offered to individuals with BMI ≥40 kg/m2, and patients with BMI ≥35 kg/m2 with an obesity associated disease, in particular diabetes mellitus type 2 (T2D). Bariatric surgery in persons with BMI < 35 kg/m2 is currently not endorsed in Swedish national guidelines (National Board of Health and Welfare, 2015). Glycaemic stabilisation is reported to occur very early after surgery, before any significant weight loss. In a recent joint statement by several international diabetes organizations, it was proposed that bariatric surgery should be considered to be an option to treat T2D in patients with BMI 30.0–34.99 kg/m2 and inadequately controlled hyperglycaemia despite optimal medical treatment. Objective: To study if bariatric surgery in patients with T2D and a BMI <35 kg/m2 is superior to standard treatment with regard to diabetes control. Search methods and study selection criteria: During January 2016 two authors performed systematic searches in PubMed, Embase, the Cochrane Library and a number of HTA-databases for systematic reviews, randomized (RCT) and non-randomised controlled studies. Due to the small number of original articles fulfilling the inclusion criteria we chose to only include and critically appraise original articles. Main results: The literature search resulted in four RCTs and six cohort studies (two reporting on the same population) comparing results of bariatric surgery with medical treatment in T2D patients with BMI <35 kg/m2. The studies had limitations mainly related to, e.g., short follow-up, some inconsistency, indirectness due to different interventions or unclear patient selection, and imprecision. Mortality was reported in two studies with only one reported death. Remission of T2D was studied in three RCTs and four cohort studies. The frequency of T2D remission during 1–3 years follow-up may be higher after bariatric surgery compared with non-surgical standard care (GRADE ⊕⊕ ). Diabetes related and cardiovascular complications were not studied. Health related quality of life (SF-36) was reported in one RCT and physical wellbeing may improve after bariatric surgery compared with medical treatment (GRADE ⊕⊕ ). Regarding glycaemic control, bariatric surgery compared with non-surgical standard care probably reduces HbA1c (GRADE ⊕⊕⊕ ), may reduce fasting plasma glucose (GRADE ⊕⊕ ) but the effect on the number of glucose-lowering medications is uncertain (GRADE ⊕ ). Bariatric surgery compared with non-surgical standard care probably reduces BMI (GRADE ⊕⊕⊕ ) but the effects on other metabolic risk factors are uncertain (GRADE ⊕ ). Risks and complications: The rate of surgical complications was reported from four to 17% ranging from mild to more severe complications requiring surgical intervention. Concluding remarks: This systematic review shows that bariatric surgery compared with medical treatment may increase the frequency of diabetes remission and probably results in improved glycaemic control in adults with overweight or obesity (BMI< 35 kg/m2, mainly 30 – 34.99 kg/m2) during 1–3 years follow-up. The bariatric surgical procedures mainly performed in Sweden today (Roux-en-Y gastric bypass, vertical sleeve gastrectomy) were investigated in only half of the current studies. Data on long term efficacy and safety are lacking and there are no results indicating reduced risk of cardiovascular disease, cancer or death. No relevant health economic analyses are available.
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- Hellebö Johanson, Else, 1969, et al.
(author)
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No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes
- 2005
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In: Diabetes Metab Res Rev. - : Wiley. - 1520-7552. ; 21:4, s. 376-81
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Journal article (peer-reviewed)abstract
- BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
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- Murdolo, Giuseppe, 1966, et al.
(author)
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Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin
- 2007
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In: J Clin Endocrinol Metab. - : The Endocrine Society. - 0021-972X. ; 92:7, s. 2688-95
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Journal article (peer-reviewed)abstract
- CONTEXT: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis. OBJECTIVES: The objectives of this study were to: 1) characterize the interstitial levels and the gene expression of MCP-1 in the sc abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial stiffness. DESIGN: Nine lean (L) and nine uncomplicated obese (OB) males were studied in the fasting state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1 and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were characterized at baseline and after hyperinsulinemia. RESULTS: OB showed elevated sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1 concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a "co-upregulation" of MCP-1, MCP-2, macrophage inflammatory protein-1alpha, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. After hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but not in OB. Finally, sMCP-1 excess in the OB positively correlated with the stiffer vasculature. CONCLUSIONS: These observations demonstrate similar interstitial concentrations and a differential gene response to hyperinsulinemia of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the SCAAT MCP-1 gene overexpression as a biomarker of an "inflamed" adipose organ and impaired glucose metabolism.
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- Rotter Sopasakis, Victoria, 1972, et al.
(author)
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High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator
- 2004
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In: Obes Res. - 1071-7323. ; 12:3, s. 454-60
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ. RESEARCH METHODS AND PROCEDURES: Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation. RESULTS: The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size. DISCUSSION: These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
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- Sandqvist, Madelene, 1974, et al.
(author)
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Decreased Permeability Surface Area for Glucose in Obese Women with Postprandial Hyperglycemia: No Effect of Phosphodiesterase-5 (PDE-5) Inhibition
- 2013
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 45:8, s. 556-560
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Journal article (peer-reviewed)abstract
- Insulin-mediated microvascular recruitment is recognized as a potential mechanism contributing to insulin resistance. In this study, we compared a marker of microvascular function, the permeability surface area for glucose (PSglu), and forearm glucose uptake after an OGTT in obese women with impaired glucose metabolism and healthy lean nondiabetic women, with the aim to characterize whether decreased permeability surface area for glucose or decreased glucose uptake may contribute to postprandial hyperglycemia in the obese group. In addition, we evaluated whether the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, in a randomized double blind placebo controlled design, might attenuate postprandial glucose levels in obese women. For these purposes, intramuscular microdialysis, blood sampling from arterial and venous blood of the forearm, and measurements of forearm blood flow were performed. The results showed an impaired permeability surface area for glucose (IAUC PSglu 31 +/- 13 vs. 124 +/- 31; p < 0.05) in obese when compared with lean participants, but no differences in forearm glucose uptake appeared between the groups. Furthermore, a single dose of tadalafil 10 mg showed no improvement of the permeability surface area for glucose, glucose uptake, or circulating glucose levels in obese participants. In conclusion, the postprandial PSglu response was impaired in obese women showing postprandial hyperglycemia, indicating a compromised microcirculation. However, we were unable to demonstrate any acute effect on either vascular function or glucose uptake of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil.
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| 8. |
- Sandqvist, Madelene, 1974, et al.
(author)
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Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males
- 2005
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 180:1, s. 119-25
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Low adipocyte IRS-1 protein expression is a biomarker for insulin resistance and early atherosclerosis. However, whether IRS-1 protein expression is related to systemic arterial stiffness, is unknown. METHODS AND RESULTS: Ten non-diabetic male subjects with low adipocyte IRS-1 protein expression (LIRS) were matched with 10 non-diabetic males with normal IRS-1 protein expression (NIRS). Augmentation index (AIx) and time for reflection of pulse wave (Tr) were studied with pulse wave analysis, both in the fasting state and during a euglycemic hyperinsulinemic clamp. The LIRS-group showed an increased fasting insulin concentration (fP-insulin 71+/-4 pmol/L versus 58+/-5 pmol/L; p=0.02 (mean+/-S.E.)), whereas glucose disposal rate during the clamp (8.7+/-0.8 mg/kg LBM/min versus 10.3+/-1.3 mg/kg LBM/min; n.s.) did not differ significantly. Blood pressure, lipid parameters, adiponectin, endothelin-1 and CRP concentrations were similar. However, in the basal state, AIx was increased (129+/-4% versus 116+/-2%; p<0.02) and Tr was decreased (150+/-3 ms versus 171+/-5 ms; p<0.01), suggesting stiffer vessels in the LIRS-group. The LIRS-group exhibited an attenuated AIx response to hyperinsulinemia compared to the NIRS-group. CONCLUSIONS: The data suggest that non-obese non-diabetic men with a low adipocyte IRS-1 protein expression have an increased systemic arterial stiffness.
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| 9. |
- Sandqvist, Madelene, 1974, et al.
(author)
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Postprandial interstitial insulin concentrations in type 2 diabetes relatives
- 2006
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In: Eur J Clin Invest. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:6, s. 383-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.
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| 10. |
- Sandqvist, Madelene, 1974
(author)
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Studies of the adipose tissue in insulin resistance with microdialysis
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Type 2 diabetes is characterized by a combination of insulin resistance and an impaired insulin secretion. Theprevalence of the disease has taken epidemic proportions, and it is therefore of great concern to characterize itspathophysiology, as well as to identify individuals with increased risk for the disease, enabling to take measuresfor prevention and cure. In the present thesis early perturbations in the abdominal adipose tissue metabolism inthe development of type 2 diabetes are characterized. Furthermore, a possible link between adipose tissuedysfunction and a risk marker for cardiovascular disease is studied.To identify early metabolic perturbations, healthy volunteers with known increased risk of developing type 2diabetes, as subjects with heredity for the disease, subjects with increased fat cell size, or subjects with a defectin the adipocyte insulin signalling system (low IRS-1 protein expression) are studied. The microdialysistechnique allows measurements of substances in the subcutaneous interstitial fluid in vivo. 133Xenon-clearancetechnique is applied for adipose tissue blood flow measurements. Subcutaneous needle biopsy is performed toallow measurement of IRS-1 protein expression by immunoblotting and measurement of fat cell size. Arterialstiffness is measured by pulse wave analysis. The euglycemic hyperinsulinemic clamp method is applied formeasurement of insulin sensitivity.In paper I the lactate release per fat cell is shown to be increased during hyperinsulinemia in subjects prone todevelop type 2 diabetes, indicating a disturbance in glucose metabolism in their subcutaneous adipocytes. Anincreased fat cell size is shown to be associated with an increased interstitial lactate concentration. In paper II anincreased fat cell size is shown to be associated with increased subcutaneous interstitial interleukin-6 (IL-6)levels in vivo, as well as increased IL-6 mRNA expression and IL-6 secretion in vitro. Increased IL-6 levels areshown to down regulate adipocyte differentiation markers in vitro, which may result in an increased fat cell size.In paper III the kinetics of transendothelial insulin transport to the adipose tissue is studied in subjects withheredity for type 2 diabetes and a decreased insulin sensitivity. The proportion of insulin passing the capillaryendothelium to the interstitium is similar at two different concentrations of physiological hyperinsulinemia,indicating that insulin action in vivo is primarily dependent on the cellular insulin sensitivity. In paper IVsubjects with a low IRS-1 protein expression in the adipocytes are shown to have an increased arterial stiffness,indicating low IRS-1 protein expression as a potential risk marker for cardiovascular disease.In conclusion, subjects prone to develop type 2 diabetes exhibit increased lactate and IL-6 levels in thesubcutaneous adipose tissue. However, the transcapillary insulin transport in the adipose tissue does not seem tobe a cause of insulin resistance in these subjects. Furthermore, an impairment in the insulin signalling cascade inthe adipocytes is identified as a risk marker for arterial stiffness.
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