| 1. |
- Adamson, Carly, et al.
(författare)
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Efficacy of Dapagliflozin in Heart Failure with Reduced Ejection Fraction According to Body Mass Index.
- 2021
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:10, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an ’obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse- outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight ($<$18.5 kg/m(2) ); normal weight (18.5-24.9 kg/m(2) ); overweight (25.0-29.9 kg/m(2) ); obesity class I (30.0-34.9 kg/m(2) ); obesity class II (35.0-39.9 kg/m(2) ); and obesity class III ($>$/=40 kg/m(2) ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal- weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P $<$ 0.001). CONCLUSION: We confirmed an ’obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 2. |
- Ahlbeck Bergendahl, Ida, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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| 3. |
- Andersson, Jan, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2015 : Resursöversikt
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser (SLU Aqua) vid Sveriges lantbruksuniversitet (SLU) samt yrkesfiskets rapportering.Rapporten omfattar 40 fiskarter uppdelade i olika bestånd, samt sex skal-och blötdjursarter.Nytt för årets upplaga är en beskrivning av hur de provfisken som ligger till grund för analys och rådgivning utförs.Översikten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten.
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| 4. |
- Andersson, Magnus, et al.
(författare)
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Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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| 5. |
- Butt, Jawad H., et al.
(författare)
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Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction : A Prespecified Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial.
- 2021
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 6:6, s. 678-689
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men. Objective: To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Design, Setting, and Participants: Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B- type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results: A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of $>$/=5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of $>$/=5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women. Conclusions and Relevance: Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.
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| 6. |
- Docherty, Kieran F, et al.
(författare)
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Effects of dapagliflozin in DAPA-HF according to background heart failure therapy.
- 2020
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:25, s. 2379-2392
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Tidskriftsartikel (refereegranskat)abstract
- In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy.In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n=4744) were treated with a diuretic (84%), renin-angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65-0.85] for the primary composite endpoint (P<0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61-0.86) compared with 0.77 (95% CI 0.63-0.94) in those not on all three of these treatments (P-interaction 0.64).The benefit of dapagliflozin was consistent regardless of background therapy for HF.
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| 7. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes
- 2010
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Ingår i: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:10, s. 2205-2208
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Recent evidence suggests that reduced synthesis of nitric oxide in endothelial cells, i.e. endothelial dysfunction, contributes to the impaired action of insulin in the vasculature of patients with type 2 diabetes. We investigated whether selective inhibition of phosphodiesterase-5 by tadalafil has beneficial effects on peripheral microcirculation and glucose uptake in these patients. Methods We enrolled seven postmenopausal women with type 2 diabetes and ten age-matched healthy women as controls in a placebo-controlled study to evaluate the acute metabolic effects of tadalafil. We performed microdialysis and blood flow measurements in muscle, and sampled arterial and deep venous blood before and after a single dose of tadalafil 20 mg or placebo. Circulating glucose and insulin levels, muscle capillary recruitment as reflected by permeability surface area for glucose (PSglu) and forearm glucose uptake were measured. Results In women with type 2 diabetes, but not in the control group, tadalafil induced increases in the incremental AUC for PSglu (tadalafil vs placebo 41±11 vs 4±2 ml [100 g]−1 min−1, p<0.05) and forearm glucose uptake (46±9 vs 8±4 µmol [100 g]−1 min−1, p<0.05). The variable that best predicted forearm glucose uptake was PSglu, which explained 70% of its variance. However, fasting glucose and insulin concentrations were similar following treatment with placebo or tadalafil in the two groups. Conclusions/interpretation This study suggests that tadalafil evokes positive metabolic effects in insulin-resistant women with type 2 diabetes.
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| 8. |
- McMurray, John J V, et al.
(författare)
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A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF).
- 2019
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.DESIGN AND METHODS: The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) is an international, multicentre, parallel group, randomized, double-blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N-terminal pro B-type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 . The trial is event-driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient-reported outcomes. A total of 4744 patients have been randomized.CONCLUSIONS: DAPA-HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.
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| 9. |
- McMurray, J. J. V., et al.
(författare)
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Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 381:21, s. 1995-2008
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.METHODS In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.RESULTS Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.CONCLUSIONS Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.
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| 10. |
- Petrie, Mark C, et al.
(författare)
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Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
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Tidskriftsartikel (refereegranskat)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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| 11. |
- Serenelli, Matteo, et al.
(författare)
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Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
- 2020
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:36, s. 3402-3418
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Tidskriftsartikel (refereegranskat)abstract
- Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110mmHg; 981≥110<120; 1149≥120<130; and 1409≥130mmHg. The placebo-corrected reduction in SBP from baseline to 2weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P<0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.ClinicalTrials.gov NCT03036124.
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| 12. |
- Sjöstrand, Mikaela, 1964
(författare)
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Insulin resistance in skeletal muscle. With special reference to interstitial insulin and glycerol
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin resistance is a central feature of type 2 diabetes and obesity and is associated with cardiovascular disease. In insulin-resistant muscle, the insulin-mediated glucose uptake is decreased.The delivery of insulin to the interstitial fluid of human skeletal muscle has previously not been investigated. The aim in this thesis was to determine the interstitial muscle insulin, glucose, and lactate concentrations in healthy subjects as well as in type 2 diabetes patients during stable hyperinsulinemia. Furthermore, the effect of insulin has a slow onset in insulin-resistant states and, therefore, the time kinetics of insulin delivery and action were investigated in obese subjects.Insulin resistance is also associated with enlarged triglyceride stores and increased lipid oxidation rates in skeletal muscle. The regulation of glycerol in the interstitial fluid of muscle was studied in healthy, obese, and type 2 diabetic subjects. The methods applied included muscle microdialysis for sampling of the interstitial fluid, the forearm technique for arterio-venous balance studies of metabolism, and the euglycemic hyperinsulinemic clamp to assess insulin sensitivity.Interstitial muscle insulin levels equaled half of the insulin concentration in plasma at steady-state hyperinsulinemia in both healthy and type 2 diabetic subjects. Insulin and glucose levels in the muscle interstitial fluid were similar in type 2 diabetes patients and their controls, but lactate in plasma and the muscle interstitial fluid was lower and the blood flow rate was decreased in these patients. In obese subjects, a delay in the delivery of interstitial insulin was demonstrated and a slow onset of the effect of insulin was confirmed. The muscle glycerol level was 2-3 times higher than plasma glycerol, while the arterio-venous glycerol concentration difference over the forearm was insignificant. The interstitial-arterial concentration difference of glycerol in muscle was not affected during insulin stimulation. In obese subjects, both interstitial and I-A concentration differences of glycerol were higher than in lean subjects, whereas type 2 diabetic subjects did not have significantly different interstitial glycerol or I-A glycerol levels than weight-matched controls. In conclusion, the capillary wall is rate limiting for insulin transport at high plasma insulin levels. It is suggested that cellular defects, rather than an insufficient delivery of insulin and glucose to the muscle interstitial fluid, are responsible for the insulin resistance in type 2 diabetes at steady-state hyperinsulinemia.The delay in insulin delivery and effect of insulin, shown in obese subjects, may contribute to insulin resistance in muscle. It is hypothesized that the decreased lactate production rates in response to insulin may contribute to the decreased blood flow rate and slow rate of insulin delivery in insulin-resistant muscle. Muscle glycerol appears to be a poor marker for muscle lipolysis since local uptake of glycerol occurs. Insulin does not seem to regulate muscle glycerol. Obesity has more impact on the interstitial muscle glycerol than the type 2 diabetes state per se.
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