Interactions of glucose metabolism and chronic heart failure.

BACKGROUND: We evaluated insulin sensitivity and beta cell function in patients with chronic heart failure (CHF), and investigated a possible correlation of these metabolic parameters with specific biomarkers of heart failure. Additionally, we investigated the effects of two angiotensin receptor blockers (ARBs), namely telmisartan and candesartan, that were administered over a 5 month treatment period, as additional therapy to standard care. METHODS AND RESULTS: The study group consisted of 94 CHF patients. Insulin sensitivity (OGIS index) and insulin secretion parameters were investigated by frequently sampled oral glucose tolerance tests and consecutive mathematical modelling. In total, 94.6 % of patients had clinically overt diabetes, impaired glucose tolerance or insulin resistance at the time of enrolment HbA1c was found to correlate to NT-proBNP, MR-proADM, CT-proET-1, and MR-proANP, but not to Copeptin. NT-proBNP correlated inversely to OGIS. None of the metabolic parameters were altered significantly after candesartan or telmisartan treatment in either the patient or standard care group. CONCLUSION: Insulin sensitivity and insulin secretion are impaired in CHF and biomarkers of heart failure and atherosclerotic disease correlate to glucose metabolism.

Glucose turnover and intima media thickness of internal carotid artery in type 2 diabetes offspring.

BACKGROUND: First-degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a approximately 40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle-aged OFF. MATERIALS AND METHODS: T2DM-OFF (n = 18, 14f/4m, 45.6 +/- 2.1 years, BMI: 26 +/- 1 kg m(-2)) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44.5 +/- 2.1 years, BMI: 24 +/- 1 kg m(-2); each P > 0.30), all with normal glucose tolerance as tested by three-hour (75 g) oral glucose tolerance tests (OGTT). Two-hour hyperinsulinaemic (40 mU min(-1).m(-2))isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D-[6,6-(2)H(2)]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI). RESULTS: Before and during OGTT, both groups were similar in plasma glucose, insulin, C-peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0.03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was approximately 38% lower (P < 0.03) in OFF who showed higher plasma FFA (44 +/- 9 micromol L(-1)) than CON (26 +/- 3 micromol L(-1), P < 0.05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0.007) reduced AI. ICA-IMT was approximately 18% higher in OFF (P < 0.002), but did not correlate with insulin sensitivity. CONCLUSION: The data obtained show middle-aged T2DM-OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin-dependent suppression of plasma FFA and increased ICA-IMT.