Both acute and chronic near-normoglycaemia are required to improve insulin resistance in Type 1 (insulin-dependent) diabetes mellitus

Fasching, Peter; Ratheiser, Klaus; Damjancic, P.; Schneider, Barbara; Nowotny, Peter; Vierhapper, H.; Waldhäusl, W.

doi:10.1007/bf00400239

Cited by 25 publications

(24 citation statements)

References 40 publications

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“…Whereas short-term near normoglycemia for 24 h only partially ameliorates the derangement of glycogen metabolism in moderately controlled type 1 diabetic subjects (7), combined long-and short-term near normoglycemia resulted in peak hepatic glycogen concentrations as well as net rates of hepatic glycogen synthesis and breakdown in type 1 diabetic patients that were identical to those of nondiabetic humans (5,30 -32). Consequently, EGP was also normal in those well-controlled type 1 diabetic patients, consistent with results of previous studies (18,19).…”

Section: Discussionsupporting

confidence: 91%

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Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

Bischof

Bernroider²,

Krššák³

et al. 2002

Diabetes

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We tested the impact of long-term near normoglycemia (HbA 1c <7% for >1 year) on glycogen metabolism in seven type 1 diabetic and seven matched nondiabetic subjects after a mixed meal. Glycemic profiles (6.2 ؎ 0.10 vs. 5.9 ؎ 0.07 mmol/l; P < 0.05) of diabetic patients were approximated to that of nondiabetic subjects by variable insulin infusion. Rates of hepatic glycogen synthesis and breakdown were calculated from the glycogen concentration time curves between 7:30 P.M. and 8:00 A.M. using in vivo 13 C nuclear magnetic resonance spectroscopy. Glucose production was determined with D-[6,6-2 H 2 ]glucose, and the hepatic uridine-diphosphate glucose pool was sampled with acetaminophen. Glycogen synthesis and breakdown as well as glucose production were identical in diabetic and healthy subjects: 7.3 ؎ 0.9 vs. 7.1 ؎ 0.7, 4.2 ؎ 0.5 vs. 3.8 ؎ 0.3, and 8.7 ؎ 0.5 vs. 8.4 ؎ 0.7 mol ⅐ kg ؊1 ⅐ min ؊1 , respectively. Although portal vein insulin concentrations were doubled, the flux through the indirect pathway of glycogen synthesis remained higher in type 1 diabetic subjects: ϳ70 vs. ϳ50%; P < 0.05. In conclusion, combined longand short-term intensified insulin substitution normalizes rates of hepatic glycogen synthesis but not the contribution of gluconeogenesis to glycogen synthesis in type 1 diabetes. Diabetes 51:49 -54, 2002 E arly studies on glycogen metabolism in type 1 diabetic patients using liver biopsies revealed controversial results, reporting either increased or decreased liver glycogen concentrations (1-4). When liver glycogen was continuously measured with 13 C nuclear magnetic resonance (NMR) spectroscopy, it became clear that under physiologic conditions of mixed meal ingestion, poorly controlled type 1 diabetic patients indeed exhibit a defect of net liver glycogen synthesis that accumulates throughout the day and is most pronounced after dinner (5). Furthermore, these authors reported higher contribution of the indirect (carbon 3 compounds 3 glucose 3 glucose-6-phosphate 3 glucose-1-phosphate 3 UDP-glucose 3 glycogen) compared with the direct pathway of glycogen synthesis (glucose 3 glucose-6-phosphate 3 glucose-1-phosphate 3 UDP-glucose 3 glycogen) (5,6). We recently found that type 1 diabetic subjects with poor metabolic control, as evidenced by an HbA 1c of ϳ9%, also present with reduced glycogen breakdown during the night after mixed meal ingestion (7). Short-term intensified insulin treatment for 24 h, resulting in near-normal plasma glucose concentrations, improved both defects in glycogen synthesis and breakdown that, however, were still ϳ52 and ϳ26% lower, respectively, compared with nondiabetic subjects.At present, even advanced insulin substitution regimens do not resemble the physiologic insulin secretion pattern, since peripheral administration of insulin distorts the portal-to-peripheral insulin gradient and thereby affects hepatic glycogen turnover (8). Furthermore, the physiologic inhibition of glucagon secretion by insulin is impaired (9), giving rise to the portal vein glucagon-to-insu...

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Section: Discussionsupporting

confidence: 91%

“…Long-and short-term near normoglycemia exerts an additive effect to decrease EGP and fasting hyperglycemia in those patients (18,19). It is conceivable that long-and short-term near normoglycemia could further improve hepatic glycogen metabolism and glucose production.…”

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confidence: 99%

Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

Bischof

Bernroider²,

Krššák³

et al. 2002

Diabetes

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“…Publications were excluded for the following reasons: no type 1 diabetes mellitus (nZ3), age of participants was below 18 years (nZ7), absence of a healthy control group (nZ5), use of a clamp technique, not comparable to the iso-or euglycemic clamp method (nZ3), no quantitative outcome measures reported (nZ7) and one publication was excluded because participants had newly onset type 1 diabetes mellitus, in whom endogenous insulin production might be partly preserved. Finally, 38 publications were included in this meta-analysis, of which five publications (11,12,13,14,15) consisted of two and one publication (16) of three studies.…”

Section: Search Resultsmentioning

confidence: 99%

Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis

Donga¹,

Dekkers²,

Corssmit³

et al. 2015

European Journal of Endocrinology

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Objective: The aim of this study was to perform a systematic review and meta-analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls, assessed by hyperinsulinemic euglycemic clamp studies. Design and methods: We conducted a systematic search of publications using PubMed, EMBASE, Web of Science and COCHRANE Library. Hyperinsulinemic euglycemic clamp studies comparing adult patients with type 1 diabetes mellitus to healthy controls were eligible. Primary outcome measures were pooled mean differences of insulin sensitivity of endogenous glucose production (EGP), of glucose uptake and of lipolysis. We estimated mean (standardized) differences and 95% CIs using random effects meta-analysis. Results: We included 38 publications in this meta-analysis. The weighed mean differences in EGP during hyperinsulinemia between patients and controls was 0.88 (95% CI: 0.47, 1.29) in the basal state and 0.52 (95% CI: 0.09, 0.95) in insulin stimulated conditions, indicating decreased hepatic insulin sensitivity in patients. Insulin sensitivity of glucose uptake was either reported as M value (M), glucose infusion rate (GIR), glucose disposal rate (GDR) or metabolic clearance rate (MCR). Weighed mean differences were similar for M K3.98 (95% CI: K4.68, K3.29) and GIR K4.61 (95% CI: K5.86, K3.53). Weighed mean difference for GDR was K2.43 (95% CI: K3.03, K1.83) and K3.29 (95% CI: K5.37, K1.22) for MCR, indicating decreased peripheral insulin sensitivity in patients. Insulin mediated inhibition of lipolysis was decreased in patients, reflected by increased non-esterified fatty acid levels. Conclusions: Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic, peripheral and adipose tissues.

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“…The similar course of plasma FFAs during OGTT also indicates comparable insulin sensitivity in the adipose tissue of all groups. This indicates that both glucotoxicity and lipotoxicity, which had certainly been present in type 1 diabetic patients with former end-stage renal failure (45,46), can be reversed after successful PKT resulting in nondiabetic glycemia.…”

Section: Insulin Sensitivitymentioning

confidence: 96%

Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation: A sign of impaired -cell function?

Stadler

2006

Diabetes Care

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OBJECTIVE -In response to hyperglycemia, ␤-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all ␤-cell hormones. RESEARCH DESIGN AND METHODS-Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, ␤-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 Ϯ 1 kg/m 2 , 47 Ϯ 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 Ϯ 1 kg/m 2 , 50 Ϯ 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 Ϯ 1 kg/m 2 , 47 Ϯ 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT).RESULTS -PKT patients had higher fasting amylin (19 Ϯ 3 vs. control subjects: 7 Ϯ 1 pmol/l) and insulin (20 Ϯ 2 vs. control subjects: 10 Ϯ 1 U/ml; each P Ͻ 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P Ͻ 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9 -31% higher (P Ͻ 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P Ͻ 0.05). OGIS was not significantly different between groups. ␤-Cell sensitivity to glucose was reduced in PKT patients (Ϫ64%, P Ͻ 0.009). Fasting plasma amylin was inversely associated with ␤-cell sensitivity to glucose (r ϭ Ϫ0.543, P Ͻ 0.004).CONCLUSIONS -After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired ␤-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired ␤-cell function in type 1 diabetic patients after PKT.

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Both acute and chronic near-normoglycaemia are required to improve insulin resistance in Type 1 (insulin-dependent) diabetes mellitus

Cited by 25 publications

References 40 publications

Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis

Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation: A sign of impaired -cell function?

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