Increased Incidence Of Diabetes Research Articles

HbA1c, fasting plasma glucose and the prediction of diabetes: Inter99, AusDiab and D.E.S.I.R.

IntroductionWith diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases. MethodsData are Danish (Inter99), Australian (AusDiab) and French (D.E.S.I.R.), with respectively 4930, 6012 and 3784 non-diabetic participants. ResultsDiabetes incidences at 5 years for Inter99 and AusDiab and at 6 years for D.E.S.I.R. were 2.3%, 3.1% and 2.4% respectively and incidences increased with baseline HbA1c and FPG. As HbA1c distributions differed between cohorts, HbA1c was standardized on D.E.S.I.R. data. Change-points where diabetes incidence increased were identified for HbA1c (%) after standardization: 5.1 (4.9–5.6) (Inter99), 5.4 (5.1–5.6) (AusDiab), 5.3 (5.1–5.7) (D.E.S.I.R.); for FPG change-points (mmol/l) were 5.1 (…–6.1) (Inter99), 5.5 (5.2–5.8) (AusDiab), no change-point for D.E.S.I.R. Using current diabetes risk criteria HbA1c≥5.7% and/or FPG≥5.6mmol/l to screen for diabetes provided high sensitivity (over 89%) and positive predictive values: 4.3%, 6.9%, and 5.9% respectively. ConclusionsHbA1c and FPG change-points predicting incident diabetes did not always exist, differed across studies, when available were generally lower than current criteria with wide confidence intervals. Using jointly HbA1c≥5.7% and/or FPG≥5.6mmol/l as a criterion for the risk of incident diabetes is appropriate.

Macrovascular angiopathy in children and adolescents with type 1 diabetes

Diabetes represents one of the most common diseases globally. Worryingly, the worldwide incidence of type 1 diabetes (T1D) is rising by 3% per year. Despite the rapid increase in diabetes incidence, recent advances in diabetes treatment have been successful in decreasing morbidity and mortality from diabetes-related retinopathy, nephropathy, and neuropathy. In contrast, there is clear evidence for the lack of improvement in mortality for cardiovascular diseases (CVDs). This emphasizes the importance of focusing childhood diabetes care strategies for the prevention of CVD in adulthood. Furthermore, although most work on diabetes and macrovascular disease relates to type 2 diabetes, it has been shown that the age-adjusted relative risk of CVD in T1D far exceeds that in type 2 diabetes. As T1D appears predominantly during childhood, those with T1D are at greater risk for coronary events early in life and require lifelong medical attention. Because of the important health effects of CVDs in children and adolescents with T1D, patients, family members, and care providers should understand the interaction of T1D and cardiovascular risk. In addition, optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional cardiovascular risk factors to optimize those well-recognized as well as new specific risk factors which are becoming available. Therefore, a complete characterization of the molecular mechanisms involved in the development and progression of macrovascular angiopathy is needed. Furthermore, as vascular abnormalities begin as early as in childhood, potentially modifiable risk factors should be identified at an early stage of vascular disease development.

Provider Practices in Prediabetes Intervention and Diabetes Prevention

A cross-sectional study was performed to determine if evidence-based research in prediabetes management is utilized in the medical office setting in an effort to reduce the incidence of type 2 diabetes, and to determine whether any particular demographic variables including body mass index (BMI) and provider type (physician and nonphysician) predict referrals for prediabetes management (P = .05). Electronic medical records (n = 82 317) were examined for International Classification of Diseases (ICD) codes and keywords disclosing a diagnosis of prediabetes. The records of individuals with diagnosed prediabetes were subsequently examined for keywords and ICD codes for lifestyle intervention. Logistic regression was utilized to determine whether any particular demographic factors significantly predicted whether medical providers will provide recommendations or referrals for lifestyle management of prediabetes. Age, BMI, and race were found to be significant predictors for recommendations/referrals, although overall rates of recommendation or referral were poor. Provider education and enhancements in organizational policy related to referral procedures and continuity of care from the clinical setting to the community health setting are crucial in promoting early interventions in prediabetes to offset the current projections for an increase in diabetes incidence.

The Incidence of Type-1 Diabetes in NOD Mice Is Modulated by Restricted Flora Not Germ-Free Conditions

In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can benefit the maturation of the postnatal immune system [11]. A widely accepted extrapolation from this data has been the notion that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. However, evidence supporting this influential concept is surprisingly limited [12]. In this study, we demonstrate that the incidence of diabetes in female NOD mice remained unchanged under germ-free conditions. By contrast, a spontaneous monoculture with a gram-positive aerobic spore-forming rod delayed the onset and reduced the incidence of diabetes. These findings challenge the view that germ-free NOD mice have increased diabetes incidence and demonstrate that modulation of intestinal microbiota can prevent the development of type-1 diabetes.

Statin-induced diabetes: perhaps, it's the tip of the iceberg

Sir, The meta-analysis by Mills et al. 1 involving 170 255 patients randomized in 76 trials reported on the efficacy and safety of statin therapy for the prevention of cardiovascular disease (CVD) and found a relative 9% increased risk in the development of incident diabetes ( P = 0.001) among subjects randomized to statins compared with placebo in the 17 trials reporting on diabetes development. It is noteworthy that the average age of the subjects in the meta-analysis was 59.6 years, average follow-up was 2.7 years and more than half of the subjects were randomized for the primary prevention of CVD. We feel that the implications of statin-induced diabetes are not trivial, but of major concern, particularly in the primary prevention of CVD when statin therapy might be used for decades in individuals at relatively low risk2; many questions need answering before statin therapy can be safely recommended across broad populations. Interestingly, a recently published meta-analysis involving 91 140 patients randomized in 13 trials3 specifically looking at the risk of incident diabetes from statin therapy also revealed a significant 9% increased relative risk of the development of diabetes over a mean overall trial period of 4 years. Disturbingly, 2 of the 13 trials demonstrated very high incidence of the development of diabetes among the statin-treated subjects. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER),4 a primary prevention trial of 1.9-year duration in subjects with a mean age of 66 years, demonstrated a significant relative increase in diabetes incidence of 26% among subjects randomized to rosuvastatin; the absolute rate of incident diabetes expressed in events per 1000 patient-years was 13 and 16 among the placebo and rosuvastatin subjects, respectively. Low-density lipoprotein (LDL) cholesterol was decreased robustly by 50% in the rosuvastatin subjects and the …

Cardiovascular disease, heart failure, chronic kidney disease and depression independently increase the risk of incident diabetes

Aims/hypothesisDiabetes increases the risk of cardiovascular disease (CVD) and heart failure, as well as other serious complications, such as renal disease and depression. However, these conditions are often present prior to diabetes diagnosis. We sought to determine whether they increase the risk of developing diabetes independent of other risk factors.MethodsWe identified 58,056 non-diabetic adults aged ≥30 years with no evidence of diabetes. Using electronic medical records, we identified the presence of four conditions at baseline (CVD, heart failure, renal disease and depression) and then estimated diabetes incidence over 5 years separately for patients with and without each of these conditions. Each incidence estimate was adjusted for baseline values of age, sex, fasting glucose, body mass index, systolic blood pressure, triacylglycerol, HDL-cholesterol, smoking and the presence of the other three conditions.ResultsPatients with CVD were 35% (95% CI 23–48%) more likely to develop diabetes after controlling for other risk factors. Heart failure was independently associated with an increase in diabetes incidence of 48% (95% CI 27–73%), and depression was associated with a 10% (95% CI 2–20%) increase. Chronic kidney disease was associated with a non-significant risk increase of 10% (95% CI –2–25%).Conclusions/interpretationComplications of diabetes are more prevalent among patients who will ultimately develop diabetes, and increase the risk of diabetes independently of other known risk factors. The apparent bidirectional relationships suggest that primary prevention of CVD may also help prevent diabetes.

Diabetic ketoacidosis at diagnosis in Austrian children in 1989–2008: a population-based analysis

The aim of the study was to analyse the prevalence of diabetic onset ketoacidosis (DKA) during a period of 20 years (1989-2008) on a population basis in the whole of Austria. A prospective population-based incidence study (1989-2008) was performed. The registered data set comprised blood glucose, pH, ketonuria and clinical symptoms of DKA at manifestation. DKA was defined as pH < 7.3 and severe DKA as pH < 7.1. Time trends were estimated using linear regression models. During the study period, 3331 children <15 years of age (1,797 boys and 1,534 girls) were registered with newly diagnosed type 1 diabetes. Of these, 1,238 (37.2%) presented with DKA, 855 (25.7%) had a mild and 383 (11.5%) a severe form, and one patient died at onset. DKA frequency was negatively associated with age at onset (p < 0.0001). In children <2 years the prevalence was 60%, with a higher risk for girls (70% vs 54% for boys, p < 0.05). Despite a significant increase in diabetes incidence in Austria during the observation period from 8.4 to 18.4/100,000 (p < 0.0001), no significant change in the prevalence of DKA at manifestation was observed. The overall frequency of DKA in children with newly diagnosed type 1 diabetes in Austria is high and has not changed during the last 20 years despite a clear increase in the manifestation rate. In particular, children less than 2 years of age have a high risk of DKA at onset.

Selenium and Vitamin E Supplementation for Cancer Prevention

To the Editor: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) by Dr Lippman and colleagues reported that selenium or vitamin E alone or in combination did not prevent prostate cancer. The negative results of this trial confirm the outcomes in the Nutritional Prevention of Cancer (NPC) Trial for those participants with the highest baseline plasma selenium concentration prior to supplementation with selenized yeast. The conclusion from both NPC and SELECT should be that daily selenium supplementation will not benefit all persons. Cancer risk reduction with selenium should be expected only in men with low or suboptimal levels prior to supplementation. A U-shaped dose-response relationship between selenium intake and cancer risk, as suggested by studies in dogs, is consistent with the results of SELECT and NPC. At baseline, the average participant in SELECT had selenium status within the trough of the U-shaped curve, ie, not low or suboptimal. After supplementation with 200 μg per day of selenium as selenomethionine, the average SELECT participant achieved selenium levels that far exceeded the high postsupplementation values of men in NPC in the highest baseline-selenium tertile. Those NPC participants experienced no prostate-cancer risk reduction and an almost 3-fold increased incidence of diabetes. In SELECT, there was no reduction in prostate-cancer risk and a statistically nonsignificant increased diabetes incidence. We therefore consider the results of SELECT and NPC to be consistent, not contradictory. We believe that it is time to move beyond the belief that any particular agent administered at the same dose to all participants will benefit the overall population and instead attempt to individualize cancer prevention. Subsets of individuals should be identified who are more likely to benefit from supplementation, such as persons with low selenium concentrations or perhaps those with the selenoprotein-P genotype that is associated with prostatecancer risk. This stance is distinct from claiming knowledge of which types of cancer will or will not be prevented by selenium.

TCF7L2 Regulates Late Events in Insulin Secretion From Pancreatic Islet β-Cells

OBJECTIVEPolymorphisms in the human TCF7L2 gene are associated with reduced insulin secretion and an increased risk of type 2 diabetes. However, the mechanisms by which TCF7L2 affect insulin secretion are still unclear. We define the effects of TCF7L2 expression level on mature β-cell function and suggest a potential mechanism for its actions.RESEARCH DESIGN AND METHODSTCF7L2 expression in rodent islets and β-cell lines was altered using RNAi or adenoviral transduction. β-Cell gene profiles were measured by quantitative real-time PCR and the effects on intracellular signaling and exocytosis by live cell imaging, electron microscopy, and patch clamp electrophysiology.RESULTSReducing TCF7L2 expression levels by RNAi decreased glucose- but not KCl-induced insulin secretion. The glucose-induced increments in both ATP/ADP ratio and cytosolic free Ca2+ concentration ([Ca2+]i) were increased compared with controls. Overexpression of TCF7L2 exerted minor inhibitory effects on glucose-regulated changes in [Ca2+]i and insulin release. Gene expression profiling in TCF7L2-silenced cells revealed increased levels of mRNA encoding syntaxin 1A but decreased Munc18–1 and ZnT8 mRNA. Whereas the number of morphologically docked vesicles was unchanged by TCF7L2 suppression, secretory granule movement increased and capacitance changes decreased, indicative of defective vesicle fusion.CONCLUSION—TCF7L2 is involved in maintaining expression of β-cell genes regulating secretory granule fusion. Defective insulin exocytosis may thus underlie increased diabetes incidence in carriers of the at-risk TCF7L2 alleles.

The Association ofENPP1K121Q with Diabetes Incidence Is Abolished by Lifestyle Modification in the Diabetes Prevention Program

Insulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q (rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes. OBJECTIVE AND INTERVENTION: We examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs. placebo in the Diabetes Prevention Program (DPP). DESIGN, SETTING, PARTICIPANTS, AND OUTCOME: We genotyped ENPP1 K121Q in 3548 DPP participants and performed Cox regression analyses using genotype, intervention, and interactions as predictors of diabetes incidence. Fasting glucose and glycated hemoglobin were higher in QQ homozygotes at baseline (P < 0.001 for both). There was a significant interaction between genotype at rs1044498 and intervention under the dominant model (P = 0.03). In analyses stratified by treatment arm, a positive association with diabetes incidence was found in Q allele carriers compared to KK homozygotes [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.08-1.76; P = 0.009] in the placebo arm (n = 996). Lifestyle modification eliminated this increased risk. These findings persisted after adjustment for body mass index and race/ethnicity. Association of ENPP1 K121Q genotype with diabetes incidence under the additive and recessive genetic models showed consistent trends [HR, 1.10 (95% CI, 0.99-1.23), P = 0.08; and HR, 1.16 (95% CI, 0.92-1.45), P = 0.20, respectively] but did not reach statistical significance. ENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk.

Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program.

OBJECTIVE— Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo.RESEARCH DESIGN AND METHODS— We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year.RESULTS— None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported ethnicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in β-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05).CONCLUSIONS— We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B.

Investigation of chloroform-methanol soluble wheat proteins and sphingolipids as potential dietary triggers of diabetes in BBdp rats

The present study is a follow-up to the study by Coleman (1990), which found that the incidence of diabetes reduced in non-obese diabetic (NOD) mice when chloroform-methanol soluble substances were removed from a cereal-based diet. We used a 2:1 chloroform–methanol (C–M) mixture to extract C–M soluble sphingolipids and proteins from wheat gluten. The C–M extract was subjected to silica gel chromatography and saponification to remove triglycerides, glycolipids and phospholipids. This sphingolipid-enriched fraction from wheat gluten was subsequently incorporated into a BioBreeding diabetes-prone (BBdp) rat diet. Five diets were fed over a 120-day period to BBdp rats: a negative control hydrolysed casein (HC) diet, a positive control National Toxicology Program 2000 (NTP 2000) diet, a wheat gluten (WG)-based diet, a WGGSLF diet containing the WG residue remaining after chloroform-methanol extraction, and a hydrolysed casein plus sphingolipid-enriched fraction (HCGSL) diet. There was a significant increase in diabetes incidence in rats fed the HC + wheat sphingolipid diet versus the HC diet at days 70 and 80 of the feeding study, but not at the end of the study (120 days). There were no significant differences in diabetes incidence in rats fed the WG diet and WG diet with sphingolipids removed. There were no significant differences in pancreatic insulitis scores or in the numbers of jejunal CD4+ and γδTCR + T cells in BBdp rats due to the dietary addition or absence of CM soluble substances from wheat gluten. Sera IFN-γ levels were significantly higher in the sphingolipid-removed WG diet group compared to the BBdp rats in the other four diet groups. Overall, the results of this study provide some evidence for a slight promotional effect of C–M soluble sphingolipids and proteins in wheat gluten on the incidence of diabetes and up-regulation of immune responses in the BBdp rat.

Influence of CD4 T cell help and Tregs in diabetes induction in RIP‐GP mice

Recently, we have developed a virus‐free protocol, which induces Type 1 Diabetes (T1D) in two different RIP‐GP strains with different disease kinetics and incidence. RIP‐GP Arm and RIP‐GP Berlin mice express the glycoprotein (GP) from the lymphocytic choriomeningitis virus (LCMV) strains Armstrong and WE, respectively, under control of the rat insulin promoter resulting in pancreatic LCMV‐GP expression. Our diabetes induction protocol induced T1D in all RIP‐GP Berlin mice seven to twelve days after treatment. In contrast, only maximally 35% of RIP‐GP Arm mice developed transient T1D from day nine onwards. We then analyzed whether LCMV‐specific Smarta CD4 T helper cells would increase diabetes incidence in RIP‐GP Arm mice and whether Smarta CD4 regulatory T cells (Tregs) would decrease T1D incidence in RIP‐GP Berlin mice. Transfer of Smarta T helper cells indeed increased T1D kinetics and incidence in RIP‐GP Arm mice whereas transfer of Smarta Tregs reduced T1D incidence in RIP‐GP Berlin mice to below 30%. In the future, we will analyze the mechanisms of how LCMV‐specific CD4 T helper and Treg cells influence T1D development in the two RIP‐GP strains.

162 - Active Dissemination of the Alberta Diabetes Surveillance System: Local Information for Local Planning.

Increasing Incidence and Prevalence of Diabetes Among Status Aboriginal Men in Rural and Urban Alberta, 1995 to 2006. JEFFREY A. JOHNSON, STEPHANIE U. VERMEULEN, GREG HUGEL, ELLEN TOTH, BRENDA R. HEMMELGARN, KELLI RALPH-CAMPBELL, MALCOLM KING. School of Public Health, University of Alberta, Edmonton, AB. Institute of Health Economics, Edmonton, AB, Department of Medicine, University of Alberta, Edmonton, AB, Department of Medicine, University of Calgary, Calgary, AB. The increase in diabetes rates among Status Aboriginal (SA) Canadians is well documented. Less is known about the epidemiology of diabetes for this population by location of residence. Trends of diabetes incidence and prevalence between SA men and women living in urban and rural areas of Alberta were compared. The Alberta Diabetes Surveillance System (ADSS) tracks diabetes population trends using diagnostic codes from administrative records from Alberta Health and Wellness (AHW) (1995 to 2006 in adults aged >20 years). Aboriginal Status was identified as registered Indians in the AHW Stakeholder Registry. Location of residence was defined by postal code. Multivariable logistic regression was used to compare prevalence and incidence rates over time, by sex and location of residence. Age-sex adjusted diabetes prevalence increased 35%, from 10.9% (10.4-11.5) in 1995 to 14.7% (14.2-15.2) in 2006 in rural SA and 22%, from 9.4% (8.5-10.3) in 1995 to 11.5% (10.9-12.1) in 2006 among urban SA. The greatest increases were for men, at 40% and 43% compared to 12% and 30% for women (p<0.0001), in urban and rural settings, respectively. SA men with urban residences had the greatest increase in diabetes incidence at 45%, from 7.4 (4.9-10.6) per 1000 in 1995 to 10.7 (8.3-13.5) per 1000 in 2006. Incidence increased 25% for SA women in urban locations, but did not significantly change for women in rural locations (p=0.109). Significant increases in incidence and prevalence of diabetes over the past decade were observed amongst the SA population in Alberta. Prevalence and incidence were highest in SA women, but these rates have increased faster in men over the past decade, regardless of where they lived. ABSTRACT #29

Increasing Incidence and Prevalence of Diabetes Among Status Aboriginal Men in Rural and Urban Alberta 1995 to 2006

Increasing Incidence and Prevalence of Diabetes Among Status Aboriginal Men in Rural and Urban Alberta, 1995 to 2006. JEFFREY A. JOHNSON, STEPHANIE U. VERMEULEN, GREG HUGEL, ELLEN TOTH, BRENDA R. HEMMELGARN, KELLI RALPH-CAMPBELL, MALCOLM KING. School of Public Health, University of Alberta, Edmonton, AB. Institute of Health Economics, Edmonton, AB, Department of Medicine, University of Alberta, Edmonton, AB, Department of Medicine, University of Calgary, Calgary, AB. The increase in diabetes rates among Status Aboriginal (SA) Canadians is well documented. Less is known about the epidemiology of diabetes for this population by location of residence. Trends of diabetes incidence and prevalence between SA men and women living in urban and rural areas of Alberta were compared. The Alberta Diabetes Surveillance System (ADSS) tracks diabetes population trends using diagnostic codes from administrative records from Alberta Health and Wellness (AHW) (1995 to 2006 in adults aged >20 years). Aboriginal Status was identified as registered Indians in the AHW Stakeholder Registry. Location of residence was defined by postal code. Multivariable logistic regression was used to compare prevalence and incidence rates over time, by sex and location of residence. Age-sex adjusted diabetes prevalence increased 35%, from 10.9% (10.4-11.5) in 1995 to 14.7% (14.2-15.2) in 2006 in rural SA and 22%, from 9.4% (8.5-10.3) in 1995 to 11.5% (10.9-12.1) in 2006 among urban SA. The greatest increases were for men, at 40% and 43% compared to 12% and 30% for women (p<0.0001), in urban and rural settings, respectively. SA men with urban residences had the greatest increase in diabetes incidence at 45%, from 7.4 (4.9-10.6) per 1000 in 1995 to 10.7 (8.3-13.5) per 1000 in 2006. Incidence increased 25% for SA women in urban locations, but did not significantly change for women in rural locations (p=0.109). Significant increases in incidence and prevalence of diabetes over the past decade were observed amongst the SA population in Alberta. Prevalence and incidence were highest in SA women, but these rates have increased faster in men over the past decade, regardless of where they lived. ABSTRACT #29

Gluten‐free but also gluten‐enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes

Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice. Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals. A significantly lower diabetes incidence (p < 0.0001) was observed in NOD mice fed gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p < 0.0001, 5.9%, n = 34). The minority of mice, which developed diabetes on all the three diabetes-protective (gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented. Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.

Fatal hyponatremia and other metabolic disturbances associated with psychotropic drug polypharmacy

To report a case of fatal hyponatremia, marked hyperglycemia, and acute pancreatitis following simultaneous administration of paroxetine, fluphenazine, haloperidol and olanzapine. A 44-year-old non-diabetic male was admitted unconsciously, with severe hyponatremia, hyperglycemia and bradypnea. The patient had a history of long-term treatment with paroxetine, fluphenazine, haloperidol and olanzapine. Upon arrival, the plasma sodium level was 104 mmol/l, and blood glucose was 940 mg/dl. The therapy consisted of ventilatory support and intensive correction of hyponatremia and hyperglycemia. 2 hours later, hypotension and refractory cardiac arrest occurred. The autopsy disclosed severe cerebral edema as cause of death, and a modest hemorrhagic pancreatitis. Paroxetine is a selective serotonin reuptake inhibitor which stimulates antidiuretic hormone (ADH) release and may cause the syndrome of inappropriate ADH secretion with consecutive hyponatremia. Fluphenazine and haloperidol may contribute to this syndrome. Fluphenazine, and particularly olanzapine are associated with an increased incidence ofdiabetes. Olanzapine has been reported as a risk factor for acute pancreatitis. The Naranjo probability scale was not applicable because of almost immediate lethal outcome. Polypharmacy increases the risk of various adverse reactions. Adverse effects of paroxetine and many anti-psychotic drugs, such as hyponatremia and hyperglycemia, should be monitored periodically to prevent complications. The role of olanzapine in the etiology of acute pancreatitis remains to be evaluated.

Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat

Non-hypercalcemic analogs of vitamin D(3) modulate the immune response through antigen-presenting cells (APCs) and activated T-cells. A large population-base case-control showed that vitamin D(3) intake significantly decreases the risk of type 1 diabetes development. The aim of this study was, therefore, to observe the in vivo effects of a vitamin D(3) analog administered to Bio Breeding (BB) rats. 1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-219, formerly Ro 26-2198) (BioXell, Milan, Italy) was administered in vivo to BB rats from days 42 to 110 of life at 0.2 microg/Kg BW. Control animals received only vehicle (olive oil, 4.8 microl/100 g BW). The animals of these two groups were subjected to insulin treatment as they became diabetic. Insulin (Humulin, 28.6 UI/day) was administered irrespective of diabetes occurrence to another group of rats for comparison. Blood glucose, insulin levels, glycosuria, degree of islet infiltration, and the expression of some antigens were observed. Results showed that the vitamin D(3) analog reduced diabetes incidence, although limitedly, in BB rats while administration of oral insulin increased diabetes incidence. In addition, the vitamin D(3) analog did not stimulate an enhancement in the expression of CD4 and CD25 in BB rats as it does in NOD mice, which may explain the failure of this as well as other antidiabetic treatments in the BB animal model of type 1 diabetes.

All Pre-Diabetes Is Not the Same: Metabolic and Vascular Risks of Impaired Fasting Glucose at 100 Versus 110 mg/dl

The dramatic increase in incidence of diabetes (1) has prompted efforts to identify individuals who have milder glucose intolerance, because early management with lifestyle change and/or medication can delay progression to diabetes with its attendant morbidity, mortality, and cost (2). It has long been recognized that impaired glucose tolerance (IGT) is a diabetes precursor, but recognition of IGT requires oral glucose tolerance tests (OGTTs), which many health care providers are reluctant to order (3). As a more convenient alternative, the American Diabetes Association has emphasized screening by measurement of fasting plasma glucose (FPG) and lowered the cutoff for abnormal FPG progressively from 140 to 125 to 110 mg/dl. However, compared with IGT, an impaired fasting glucose (IFG) cutoff of 110 mg/dl provided good specificity but reduced sensitivity for detecting risk of developing diabetes (4–6). To obtain increased sensitivity, the American Diabetes Association recently lowered the cutoff for IFG from 110 to 100 mg/dl (7), and application of this cutoff has increased the number of Americans thought to have “pre-diabetes” to 41 million (8). Although such individuals are considered candidates for management aimed at decreasing their risk of progressing to diabetes (9), the metabolic and cardiovascular risks of individuals with very modest abnormalities in FPG are not well understood. In this study, we compared measures of risk in individuals with fasting glucose 100–109 mg/dl (IFG100) with those with fasting glucose 110–125 mg/dl (IFG110). The …

Antihypertensive Drugs and Risk for Diabetes

In several studies, thiazide diuretics and β-blockers have been associated with increased incidence of diabetes. Now, researchers have examined this