Altered islet Beta-cell function before the onset of Type 1 (insulin-dependent) diabetes mellitus

Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p<0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p<0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p<0.0001), and total insulin responses at 0.1 g/kg (p<0.05) and 0.5 g/kg (p<0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R²) than control subjects (p<0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R² and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R² and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.     

Baclofen,a gamma-aminobutyric acid-b receptor agonist,delays diabetes onset in the non-obese diabetic mouse

Glutamic acid decarboxylase (GAD) is the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). GAD has been identified as a 64-kDa antigen expressed in pancreatic beta-cells, to which autoantibodies are generated prior to the onset of type 1 (insulin-dependent) diabetes mellitus. GAD may therefore be an initiating factor in beta-cell destruction. We administered baclofen, a GABA-B receptor agonist, to non-obese diabetic (NOD) mice in an attempt to down-regulate GAD expression and thereby reduce the incidence of diabetes. Twenty-four female NOD mice were given baclofen in their drinking water at a final dose of 50 mg/kg body weight daily from weaning to 30 weeks of age. Twentyfour sex-and litter-matched mice were used as controls. At 30 weeks there was no difference in the incidence of diabetes in the treated group compared with the controls. However, there was a significant delay in the onset of diabetes in the treated group (P<0.001, parallelism test). The degree of insulitis and the GAD activity in the pancreas per mg of protein were unchanged by baclofen treatment with respect to controls. These results suggest that baclofen may be effective in delaying diabetes onset in NOD mice by stimulating GABA activity, as this neurotransmitter, localised in the islets, may modulate insulin secretion and the antigen expression associated with it.     

Do self‐efficacy and depression predict oral impacts on daily performances across time? A 2‐yr follow‐up of students in Tanzania

This study aimed to assess the longitudinal validity of the oral impacts on daily performance (OIDP) and to identify psychosocial determinants, in terms of self‐efficacy and depressive symptoms, of the OIDP across time. Following conceptual frameworks of oral health, it was hypothesized that sociodemographic, clinical, and psychosocial factors predict oral impacts across time at both population‐ averaged and person‐specific levels. Whether the effects of sociodemographic and clinical factors were accounted for, totally or in part, by psychosocial factors were also investigated. Self administered questionnaires and oral clinical examinations at baseline (2009) and follow‐up (2011) were completed by 1,714 and 727 secondary school students, respectively. Generalized equalized equations and a random intercept model were used to account for the dependency in repeated observations. Mean OIDP change scores were negative (worsened) among those who reported worsened self‐reported oral health. Psychosocial, clinical, and sociodemographic factors were independently associated with oral impacts at the population‐averaged and person‐specific levels. Mediation of sociodemographic and clinical variables according to psychosocial variables was not observed. Satisfactory longitudinal evaluative properties of the OIDP, and independent effects of psychosocial factors on oral impacts across time, were confirmed among secondary school students in Tanzania.     

Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM

Summary To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-), T helper 2 (interleukin-4 and inter-leukin-10) lymphocytes and macrophages (tumour necrosis factor-, interleukin-1 and interleukin-1 ) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-, tumour necrosis factor- and interleukin-1 than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p<0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor- levels (p<0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor- and interleukin-1 were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p<0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.Abbreviations IL Interleukin - IFN- interferon-gamma - T_H T helper - ICA islet-cell antibody - GAD glutamic acid decar-boxylase - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - TNF- tumour necrosis factor-alpha - CTLL-16 murine cytotoxic cell line     

Sachet Water Quality and Brand Reputation in Two Low-Income Urban Communities in Greater Accra,Ghana

Sachet water has become an important primary source of drinking water in western Africa, but little is known about bacteriologic quality and improvements to quality control given the recent, rapid evolution of this industry. This report examines basic bacteriologic indicators for 60 sachet water samples from two very low-income communities in Accra, Ghana, and explores the relationship between local perceptions of brand quality and bacteriologic quality after controlling for characteristics of the vending environment. No fecal contamination was detected in any sample, and 82% of total heterotrophic bacteria counts were below the recommended limit for packaged water. Sachets from brands with a positive reputation for quality were 90% less likely to present any level of total heterotrophic bacteria after controlling for confounding factors. These results contrast with much of the recent sachet water quality literature and may indicate substantial progress in sachet water regulation and quality control.