BackgroundDiabetes mellitus (DM) is associated with high mortality, morbidity, poor general health, and loss of health-related quality of life (HRQOL). The objective of the study was to assess the factors associated with HRQOL among patients with type 2 diabetes mellitus (T2DM).MethodsThis was a cross sectional study conducted among 283 T2DM patients during June 2011 and September 2012 at a major tertiary hospital in Riyadh, Saudi Arabia. The respondents were purposively and conveniently selected according to their availability during their routine visit to the outpatient clinics and they were interviewed using the Arabic version of the Short-Form 36-item survey (SF-36) to assess the HRQOL.ResultsThe mean age of the participants was 56.4±13.2 years. Around 63% (178) were males and 37% (105) were females. Glycosylated hemoglobin level was found to be significantly higher among female and HRQOL was higher among male. Respondents who were more than 50 years old had poor HRQOL than less than 50 years age group. Poor economic status, reported diabetic complications and longer duration of diabetes were significantly associated with poor HRQOL. The respondents treated with combination of therapies (oral medication plus insulin) indicated better HRQOL than patients with insulin therapy alone. Multivariate analysis indicated that gender, economic status (except subscale energy), and complications of DM (except subscale energy) as independent risk factor for HRQOL.ConclusionGender, economic status, and complication of DM were independent risk factors for majority of the subscales of HRQOL.

Glucocorticoid concentrations vary throughout the day. To determine whether an increase in cortisol similar to that present during sleep is of physiologic significance in humans, we studied the disposition of a mixed meal when the nocturnal rise in cortisol was mimicked or prevented using metyrapone plus either a variable or constant hydrocortisone infusion. When glucose concentrations were matched with a glucose infusion, hepatic glucose release (2.6±0.2 vs. 1.5±0.4 nmol/kg per 6 h) was higher (P < 0.05) while glucose disappearance (5.9±0.3 vs. 7.3±0.9 mmol/kg per 6 h) and forearm arteriovenous glucose difference (64±24 vs. 231±62 mmol/dl per 6 h) were lower (P < 0.05) during the variable than basal infusion. The greater hepatic response during the variable cortisol infusion was mediated (at least in part) by inhibition of insulin and stimulation of glucagon secretion as reflected by lower (P < 0.05) C-peptide (0.29±0.01 vs. 0.38±0.04 mmol/ liter per 6 h) and higher (P < 0.05) glucagon (42.7±2.0 vs. 39.3±1.8 ng/ml per 6 h) concentrations. In contrast, the decreased rates of glucose uptake appeared to result from a state of "physiologic" insulin resistance. The variable cortisol infusion also increased (P < 0.05) postprandial palmitate appearance as well as palmitate, f0-hydroxybutyrate, and alanine concentrations, suggesting stimulation of lipolysis, ketogenesis, and proteolysis. We conclude that the circadian variation in cortisol concentration is of physiologic significance in normal humans. (J. Clin. Invest.

While it is well established that people with non-insulin dependent diabetes mellitus have defects in both insulin secretion and action, the relative contribution of each to glucose intolerance is not known. Therefore, nondiabetic (lean and obese) and non-insulin dependent diabetes mellitus subjects were studied on two occasions. On each occasion, insulin secretion was inhibited with somatostatin and glucose was infused in a pattern and amount that mimicked the systemic delivery rate normally observed after ingestion of 50 g of glucose. Insulin also was infused so as to mimic postprandial insulin profiles observed in separate groups of diabetic and nondiabetic subjects after food ingestion. Glucose turnover was measured using the isotope dilution method. A delayed pattern of insulin delivery (i.e., a "diabetic" insulin profile) led to higher ( P Ͻ 0.05) glucose concentrations in all groups; however, the effects were transient, resulting in only a modest increase in the integrated glycemic responses. An isolated defect in insulin action had little effect on peak glucose concentration; however, it prolonged the duration of hyperglycemia, leading to a 2.5-4.2-fold increase ( P Ͻ 0.05) in the integrated glycemic response. A combined defect in the pattern of insulin secretion and action was additive rather than synergistic. Both defects caused hyperglycemia by altering suppression of endogenous glucose release and stimulation of glucose disposal. Whereas obese diabetic and nondiabetic subjects had comparable defects in glucose clearance, non-insulin dependent diabetes mellitus subjects also had defects in hepatic insulin action. Thus, abnormalities in the pattern of insulin secretion and action alone or in combination impair glucose tolerance. An isolated defect in insulin action has a more pronounced and prolonged effect than does an isolated change in the pattern of insulin secretion. Hepatic and extrahepatic insulin resistance results in marked and sustained hyperglycemia.

SummaryCarbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-3HI glucose and [6-3H] glucose on two occasions. [6-14C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time ("constant glucagon") or 2 h following ("suppressed glucagon") glucose ingestion. This resulted in lower (p < 0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63 + 1 vs 108 + 2 pg/ ml). Lack of suppression of glucagon led to higher (p < 0.01) postprandial glucose concentrations (10.3+0.9 vs 8.1+0.7mmol/1) and a greater (p < 0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p < 0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-3H] glucose (2.6 + 0.2 vs 2.0 + 0.2 mmol-kg -1 per 6 h) or [2-3H] glucose (3.0 + 0.3 vs 2.4 + 0.2 mmol-kg -1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM. [Diabetologia (1995) 38: 337-343]

We have come a long way in our understanding of the epidemiology, pathophysiology, and clinical significance of albuminuria in patients with NIDDM. However, substantial gaps remain to be defined. NIDDM nephropathy is a serious and increasingly burdensome disease for both the diabetic individual and the society at large. Onset of microalbuminuria, an early but common manifestation of NIDDM nephropathy, marks an ominous turn for the NIDDM patient, in whom its development forecasts a grave cardiovascular outcome. Interception of albuminuria with antihypertensive agents such as ACE inhibitors in otherwise healthy NIDDM subjects holds a significant promise but must first await further investigation.