Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion.

AIMS: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). METHODS: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP). RESULTS: Both syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP. CONCLUSIONS: A distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.

High Incidence of Adverse Outcomes in Haemodialysis Patients with Diabetes with or without Diabetic Foot Syndrome: A 5-Year Observational Study in Lleida, Spain.

BACKGROUND: We evaluated whether, in subjects receiving haemodialysis (HD), the presence of diabetic foot syndrome (DFS) was associated with increased mortality compared with subjects with diabetes mellitus (DM) without DFS and with non-diabetic subjects. METHODS: Retrospective, observational study in 220 subjects followed for six years. We calculated and compared the frequency and 5-year cumulative incidence of all-cause mortality, cardiovascular (CV) mortality, CV events, major adverse CV events (MACE), and new foot ulcer (FU) or amputation. We also examined prognostic factors of all-cause and CV mortality based on baseline characteristics. RESULTS: DM patients had a 1.98 times higher probability of all-cause mortality than those without DM (p = 0.001) and 2.42 times higher likelihood of CV mortality and new FU or amputation (p = 0.002 and p = 0.008, respectively). In the DM cohort, only the risk of a new FU or amputation was 2.69 times higher among those with previous DFS (p = 0.021). In patients with DM, older age was the only predictor of all-cause and CV mortality (p = 0.001 and p = 0.014, respectively). CONCLUSIONS: Although all-cause and CV mortality were increased on HD subjects with DM, the presence of DFS did not modify the excess risk. Additional studies are warranted to further explore the impact of DFS in subjects with DM undergoing HD.

Prevalence of Diabetic Foot Disease in Patients with Diabetes Mellitus under Renal Replacement Therapy in Lleida, Spain.

Aim. To assess the prevalence of diabetic foot and other associated conditions in patients with diabetes mellitus under renal replacement in the region of Lleida, Spain. Methods. This was an observational, cross-sectional study of 92 dialysis-treated diabetic patients. Besides a podiatric examination, we explored the presence of cardiovascular risk factors, late diabetes complications, including peripheral neuropathy, atherosclerotic disease, and peripheral artery disease. We assessed risk factors for foot ulceration and amputation by logistic regression. Results. Prevalent diabetic foot was found in 17.4% of patients, foot deformities were found in 54.3%, previous ulcer was found in 19.6%, and amputations were found in 16.3%; and 87% of them had some risk of suffering diabetic foot in the future. We observed a high prevalence of patients with peripheral neuropathy and peripheral artery disease (89.1% and 64.2%, resp.). Multivariable analysis identified diabetic retinopathy and advanced atherosclerotic disease (stenosing carotid plaques) as independent risk factors for foot ulceration (p = 0.004 and p = 0.023, resp.) and diabetic retinopathy also as an independent risk factor for lower-limb amputations (p = 0.013). Moreover, there was a temporal association between the initiation of dialysis and the incidence of amputations. Conclusion. Diabetic patients receiving dialysis therapy are at high risk of foot complications and should receive appropriate and intensive foot care.

Despite higher body fat content, Ecuadorian subjects with Laron syndrome have less insulin resistance and lower incidence of diabetes than their relatives.

In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research. Among the hormonal factors implicated, we selected obesity-driven insulin resistance for further evaluation. It is known that growth hormone (GH) has profound effects on carbohydrate metabolism. In consequence, we compared the effects of the lack of the counter-regulatory effects of GH, in a group of subjects with GH receptor deficiency (GHRD) due to a mutated GH receptor vs. that of their normal relatives. It was found that, despite their obesity, subjects with GHRD, have diminished incidence of diabetes, lower glucose and insulin concentrations, and lower values of indexes indicative of insulin resistance such as HOMA-IR. The GHRD subjects were also capable of appropriately handling glucose or mixed meal loads despite diminished insulin secretion. These observations allow us to suggest that the association of obesity with increased risk for diabetes appears to be dependent on intact growth hormone signaling.