Insulin Metabolism In Patients Research Articles

Lipoatrophic diabetes in familial partial lipodystrophy type 2: From insulin resistance to diabetes

Subjects with Familial Partial Lipodystrophy type 2 (FPLD2) are at high risk to develop diabetes. To better understand the natural history and variability of this disease, we studied glucose tolerance, insulin response to an oral glucose load, and metabolic markers in the largest cohort to date of subjects with FPLD2 due to the same LMNA variant. A total of 102 patients aged > 18 years, with FPLD2 due to the LMNA 'Reunionese' variant p.(Thr655Asnfs*49) and 22 unaffected adult relatives with normal glucose tolerance (NGT) were enrolled. Oral Glucose Tolerance Tests (OGTT) with calculation of derived insulin sensitivity and secretion markers, and measurements of HbA1c, C-reactive protein, leptin, adiponectin and lipid profile were performed. In patients with FPLD2: 65% had either diabetes (41%) or prediabetes (24%) despite their young age (median: 39.5 years IQR 29.0-50.8) and close-to-normal BMI (median: 25.5 kg/m2 IQR 23.1-29.4). Post-load OGTT values revealed insulin resistance and increased insulin secretion in patients with FPLD2 and NGT, whereas patients with diabetes were characterized by decreased insulin secretion. Impaired glucose tolerance with normal fasting glucose was present in 86% of patients with prediabetes. Adiponectin levels were decreased in all subjects with FPLD2 and correlated with insulin sensitivity markers. OGTT reveals early alterations of glucose and insulin metabolism in patients with FPLD2, and should be systematically performed before excluding a diagnosis of prediabetes or diabetes to adapt medical care. Decreased adiponectin is an early marker of the disease. Adiponectin replacement therapy warrants further study in FPLD2.

Effect of Proton-Pump Inhibitors on Glucose and Insulin Metabolism on Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Some studies have revealed an improvement in glucose metabolism after proton-pump inhibitors (PPI) therapy; however, this evidence is inconclusive and limited. The study aimed to examine the effect of PPI on glucose and insulin metabolism in patients with type 2 diabetes through a systematic review and meta-analysis. Only randomized controlled trials evaluating the impact of PPI on glucose or insulin concentrations in type 2 diabetes were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A meta-analysis was conducted using a random-effects model and generic inverse variance method. Sensitivity analysis was performed using the leave-one-out method. Meta-analysis revealed no significant effect of PPI intervention on fasting glucose (mean difference [MD] -11.42 [95% CI, -29.68 to 6.83], I2 = 80%, p = 0.22), fasting insulin (MD 1.51 [95% CI, -0.36 to 3.37], I2 = 32%, p = 0.11), HOMA-IR (MD -0.16 [-0.98 to 0.65], I2 = 0%, p = 0.70), HOMA-β (MD 19.97 [-21.59 to 61.52], I2 = 71%, p = 0.35), and HbA1c concentrations (MD -0.34 [-0.99 to 0.31], I2 = 89%, p = 0.30). The treatment with PPI, in the short term, had no significant effects on glucose and insulin metabolism in patients with type 2 diabetes.

Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.

Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.

1888-P: Impaired Insulin Clearance Relates to Increased Liver Fat Content in Recent-Onset Type 2 Diabetes and to Impaired Glucose Control in Recent-Onset Type 1 Diabetes

Hepatic insulin metabolism in patients with newly diagnosed diabetes is not yet understood. Insulin clearance seems to be decreased in patients with obesity, visceral adiposity and type 2 diabetes (T2D), but data compared to glucose tolerant humans have been inconclusive. To this end, persons with type 1 diabetes (T1D; n=124) or type 2 diabetes (T2D; n=401) and glucose-tolerant humans (CON; n=245) underwent hyperinsulinemic-euglycemic clamps to assess insulin sensitivity (IS) and whole-body insulin clearance (ICWBIC, ml x kg-1 x min-1). Hepatic insulin clearance was also calculated from the ratio of the areas under the curve of plasma C-peptide and insulin (0-60 min) during intravenous glucose-tolerance test (IVGTT, 0-60 min) and mixed meal tolerance test (MMTT, 0-180 min). Hepatocellular lipid content (HCL) was measured by 1H-magnetic resonance spectroscopy. Analyses were adjusted for age, sex and BMI. In T1D, ICIVGTT (1.71±1.1 vs. 2.3±0.3 and 3.2±0.3, all p<0.05) as well as ICMMT (1.6±0.7 vs. 2.0±0.4 and 2.1±0.3, all p<0.05) were lowest compared to T2D and CON respectively and correlated negatively with HbA1c (r=-0.242 and r=-0.279, both p<0.05). In T2D, ICIVGTT was positively correlated with HbA1c (r=0.178, p<0.05) as well as with IS (r=0.242, p<0.05). T2D patients with hepatic steatosis (n=73) had lower ICIVGTT, ICWBIC as well as ICMMT (2.2±0.31 vs. 2.4±0.31, 1.4±0.4 vs. 1.5±0.4 and 1.9 ±0.3 vs. 2.1±0.2 respectively, (i.e., differences of 8%, 9% and 7%, all p<0.05) compared to T2D without steatosis (n=53). CON with steatosis also had lower ICIVGTT (n=103, 2.1±0.2 vs. 2.3±0.35, p<0.05). ICMMT positively correlated with IS (r=0.338 and r=0.187, both p<0.05) in T1D and T2D, but not in CON. In conclusion, glycemic control likely impairs insulin clearance particularly in T1D patients, whereas steatosis affects insulin clearance in T2D and in glucose tolerant humans. Disclosure S. Antoniou: None. O.P. Zaharia: None. K. Strassburger: None. Y. Karusheva: None. K. Bodis: None. Y. Kupriyanova: None. V. Burkart: None. K. Muessig: None. A. Gastaldelli: Consultant; Self; A. Menarini Diagnostics, Eli Lilly and Company, Genentech, Inc., Gilead Sciences, Inc., Inventiva Pharma. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. J. Szendroedi: None.

096. The Impact of Anti-Tumour Necrosis Factor Alpha Therapy on Platelet Function, Lipid Profile, and Insulin Metabolism in Patients with Inflammatory Arthritis: A Prospective Cohort Study

096. The Impact of Anti-Tumour Necrosis Factor Alpha Therapy on Platelet Function, Lipid Profile, and Insulin Metabolism in Patients with Inflammatory Arthritis: A Prospective Cohort Study

Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension

Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon-occluded retrograde transvenous obliteration (B-RTO) can affect glucose and insulin metabolism in patients with LC. Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh's class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure. Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of β-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure. Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.

Application of an Insulin Analogue in Six Hypoglycemia-Prone Hemodialysis Patients with Type 2 Diabetes

Day-to-day insulin requirements often change due to subtle variations in insulin metabolism in patients with type 2 diabetes undergoing hemodialysis. In such cases, intra-hemodialysis hypoglycemia frequently occurs and is a main factor interfering with the delivery of dialysis. As a result, it reduces the quality of life in patients undergoing hemodialysis. The long-acting insulin analogue glargine provides peakless, continuous release over 24 h that approximates a normal basal insulin pattern. Because it has no peak, its use in patients with diabetes undergoing hemodialysis would hypothetically be useful. Specifically, patients would be able to avoid intra-hemodialysis hypoglycemia without the necessity of skipping insulin administration on the day of hemodialysis and achieving adequate glucose control on other days. We recently experienced six cases that switched from treatment with intermediate-acting insulin to a long-acting insulin analogue, which provided better glycemic control by reducing hypoglycemia risk. Limited data are available in the literature concerning insulin analogue usage in patients with diabetes undergoing hemodialysis. Our experience suggests a large-scale prospective investigation is required on this issue. (Korean J Med 2012; 83:647-653)

Plasma adrenomedullin levels in patients with polycystic ovary syndrome

To evaluate adrenomedullin levels in patients with polycystic ovary syndrome (PCOS). Prospective study. Department of obstetrics and gynecology in a university hospital. Thirty-eight women with PCOS and 29 healthy control subjects were enrolled in the study. Plasma adrenomedullin, serum androstenedione, free T, T, DHEAS, SHBG, thyrotropin, PRL, FSH, LH, and E2 were measured in each subject. Insulin resistance was estimated by fasting insulin level, fasting glucose:insulin ratio and 75-g glucose tolerance test for 2 hours. Plasma adrenomedullin levels and correlations among adrenomedullin and gonadotropins, female sex steroids, androgens, and insulin resistance. There was no significant difference concerning plasma adrenomedullin concentrations between the groups. In patients with PCOS, fasting glucose, fasting insulin, body mass index, and free T were inversely correlated with the plasma adrenomedullin. Plasma adrenomedullin was significantly correlated with glucose:insulin ratio. After controlling for body mass index, there were no significant correlations between the above-mentioned parameters. Adrenomedullin may play a role in regulating the insulin metabolism in patients with PCOS.

Glucose and insulin metabolism in patients with hyperthyroidism due to Graves' disease.

To clarify the impairment of carbohydrate metabolism in hyperthyroidism, we performed the oral glucose tolerance test (OGTT) and glucagon tolerance test in ten patients with hyperthyroidism due to Graves' disease (GD) and in ten normal subjects. During OGTT, glucose and insulin values in the GD patients were twice as high as those in the normals. The ratio of cumulative net plasma glucose [sigma PG (0-120 minutes)] and insulin [sigma IRI (0-120 minutes)] was 0.83 +/- 0.14 and 1.14 +/- 0.25 in the GD patients and normals, respectively. During the glucagon tolerance test, plasma glucose showed lower peaks in the GD patients than in the normals. C-peptide reached a peak value at 6 min in the GD patients and at 10 min in the normals. Cyclic AMP response in the GD patients was three times greater than that in the normals. A smaller insulinogenic index and a smaller sigma PG/sigma IRI ratio in the GD patients suggest that the secretion of insulin in GD patients does not meet the demand despite the higher insulin values observed during OGTT. Greater response of cAMP, smaller and earlier peaks of C-peptide and smaller response of glucose to glucagon in the GD patients may suggest a rapid insulin turnover and a reduction of glycogen storage in the liver with hyperthyroidism.

Disordered glucose and insulin metabolism in patients with insulinoma

Disordered glucose and insulin metabolism in patients with insulinoma

Disordered Glucose and Insulin Metabolism in Patients With Insulinoma

The response of plasma glucose and insulin to infusion of glucose and of epinephrine plus propranolol were examined in normal subjects and in two patients with surgically proven insulin-secreting islet cell tumors. The plasma immunoreactive insulin concentration in the two patients was both inappropriate and independent of the plasma glucose concentration. Their insulin secretion was neither increased by physiologic stimulants nor decreased by pharmacologic inhibitors of insulin secretion. There are diagnostic uses for these data as well as theoretical implications. We propose a physiological approach to establish the diagnosis of insulin-secreting islet cell tumors.