Coffee consumption and the risk of latent autoimmune diabetes in adults--results from a Swedish case-control study.

AIMS: Coffee consumption is associated with a reduced risk of Type 2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type 2 diabetes. METHODS: We used data from a population-based case-control study with incident cases of adult onset (≥ 35 years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type 2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type 2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes. RESULTS: Coffee intake was inversely associated with Type 2 diabetes (odds ratio 0.92, 95% CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio 1.04, 95% CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio 1.11, 95% CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P = 0.0268) increase in glutamic acid decarboxylase antibody levels. CONCLUSIONS: Our findings confirm that coffee consumption is associated with a reduced risk of Type 2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type 1-like latent autoimmune diabetes in adults.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. METHODS: The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. RESULTS: Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Narrowband ultraviolet B three times per week is more effective in treating vitamin D deficiency than 1600 IU oral vitamin D3 per day: a randomized clinical trial.

BACKGROUND: It is known that narrowband ultraviolet B (NB-UVB) radiation and oral vitamin D(3) supplementation can both improve serum levels of vitamin D, expressed as 25-hydroxyvitamin D(3) [25(OH)D(3) ]. However, surprisingly few studies have compared the effects of the two interventions in treating vitamin D deficiency. OBJECTIVES: To compare the effect of NB-UVB exposure with oral vitamin D(3) supplementation on vitamin D levels in patients with vitamin D deficiency. METHODS: Seventy-three participants with vitamin D deficiency [25(OH)D(3) ≤ 25 nmol L(-1) ] were consecutively enrolled from February 2010 to May 2011, avoiding the summer period (June to September). The participants were randomized into two groups, one receiving full body NB-UVB exposure three times per week, the other receiving 1600 IU (40 µg) oral vitamin D(3) per day together with 1,000 mg calcium. Thirty-two participants completed the 6-week study period, 16 in each group. In both groups blood samples were obtained at baseline and after 3 and 6 weeks. RESULTS: We found a significantly greater increase in 25(OH)D(3) levels (mean) in the NB-UVB treated group (from 19·2 to 75 nmol L(-1) ) compared with the oral vitamin D(3) treated group (from 23·3 to 60·6 nmol L(-1) ) after 6 weeks of treatment (P = 0·02), accompanied by a significant decrease in parathyroid hormone for the whole group (from 5·3 to 4·2 pmol L(-1) , P = 0·028). CONCLUSIONS: Full body NB-UVB three times per week is more effective in treating vitamin D deficiency than prescription of a daily oral intake of 1600 IU (40 µg) vitamin D(3) .

Independent measures of insulin secretion and insulin sensitivity during the same test: the glucagon-insulin tolerance test.

BACKGROUND: To validate a test for independent assessment of insulin secretion and insulin sensitivity during the same occasion for metabolic studies in clinical practice, i.e. combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). SUBJECTS AND METHODS: We measured C-peptide response to 0.5 mg of intravenous glucagon followed 30 min later by administration of 0.05 U kg(-1) insulin (insulin tolerance test, ITT). Ten subjects with normal glucose tolerance participated on different days in an ITT, glucagon-C-peptide test, ITT followed by glucagon-C-peptide test and glucagon-C-peptide test followed by ITT to establish whether and how the tests could be combined. The test was then repeated in nine patients with type 2 diabetes to investigate its reproducibility. In 20 subjects with varying degrees of glucose tolerance, the test was compared with the Botnia clamp (an intravenous glucose tolerance test combined with a euglycaemic hyperinsulinemic clamp). RESULTS: When ITT preceded the glucagon test, C-peptide response was blunted. Therefore, we first administered glucagon and then insulin (GITT). The K(ITT) from the GITT was reproducible (CV = 13 %) and correlated strongly with the glucose disposal rate from the Botnia clamp (r = 0.87, r(2) = 0.75, P < 0.001). The C-peptide response to glucagon was reproducible (CV = 13 %). The disposition index, providing a measure of beta-cell function adjusted for insulin sensitivity, calculated from the GITT showed good discrimination between individuals with varying degrees of glucose tolerance. CONCLUSIONS: The GITT provides simple, reproducible and independent estimates of insulin sensitivity and secretion on the same occasion for metabolic studies in individuals with normal and abnormal glucose tolerance.

Fatty fish consumption and risk of latent autoimmune diabetes in adults.

OBJECTIVE: It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA). METHODS: Analyses were based on data from a Swedish case-control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat. RESULTS: Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30-0.87, and 1.01, 95% CI 0.74-1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35-1.03, type 2 diabetes: OR 1.14, 95% CI 0.79-1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19-1.12, type 2 diabetes: OR 1.58, 95% CI 1.08-2.31). CONCLUSIONS: Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly through effects of marine-originated omega-3 fatty acids.

Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes.

OBJECTIVES: To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention. DESIGN AND SETTING: Prospective open-label study of 54 patients with type 2 diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone. RESULTS: HbA1c decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving levels<6.5%. However, in the group followed for another 3 months HbA1c increased (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001). CONCLUSIONS: Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving beta-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.