We investigated whether parental history of type 2 diabetes mellitus (T2D) is associated with age, lifestyle, anthropometric factors, and clinical severity at the time of T2D diagnosis.
We conducted a cross-sectional study based on the Danish Centre for Strategic Research in Type 2 Diabetes cohort. We examined the prevalence ratios (PR) of demographic, lifestyle, anthropometric, and clinical factors according to parental history, using Poisson regression adjusting for age and gender.
Of 2825 T2D patients, 34% (n?=?964) had a parental history of T2D. Parental history was associated with younger age at diagnosis [adjusted (a)PR 1.66, 95% confidence interval: 1.19, 2.31) for age
Nocturnal hypoglycemia is a feared complication to insulin treated diabetes. Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia. EEG changes are demonstrated during daytime hypoglycemia. In this explorative study, we test the hypothesis that specific hypoglycemia-associated EEG-changes occur during sleep and are detectable in time for the patient to take action.
Ten patients with type 1 diabetes (duration 23.7 years) with IAH were exposed to insulin-induced hypoglycemia during the daytime and during sleep. EEG was recorded and analyzed real-time by an automated multi-parameter algorithm. Participants received an auditory alarm when EEG changes met a predefined threshold, and were instructed to consume a meal.
Seven out of eight participants developed hypoglycemia-associated EEG changes during daytime. During sleep, nine out of ten developed EEG changes (mean BG 2.0 mmol/l). Eight were awakened by the alarm. Four corrected hypoglycemia (mean BG 2.2 mmol/l), while four (mean BG 1.9 mmol/l) received glucose infusion. Two had false alarms. EEG-changes occurred irrespective of sleep stage. Post hoc improvement indicates the possibility of earlier detection of hypoglycemia.
Continuous EEG monitoring and automated real-time analysis may constitute a novel technique for a hypoglycemia alarm in patients with IAH.
OBJECTIVE: Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes. We therefore treated young, glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity, glucose metabolism, and glycogen synthase activity. RESEARCH DESIGN AND METHODS: Relatives were randomized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo. Before and after treatment, an oral glucose tolerance test (OGTT) and a euglycemic-hyperinsulinemic clamp (40 mU. m(-2). min(-1)) were performed, including 3-(3)H glucose infusion, glycolytic flux calculations, indirect calorimetry, and muscle biopsies. RESULTS: Twelve relatives received troglitazone and 12 placebo (aged 30.8 +/- 2.0 vs. 30.3 +/- 1.6 years, BMI 29.6 +/- 0.8 vs. 30.5 +/- 1.3 kg/m(2); means +/- SE). Area under the curve (AUC) for plasma glucose at the second OGTT was unchanged after troglitazone. In contrast, troglitazone reduced fasting (from 70.3 +/- 6.9 to 52.2 +/- 5.8 vs. 73.6 +/- 11.0 to 73.3 +/- 6.5 pmol/l, P
OBJECTIVE: To evaluate the quality of diabetes care achieved on the process and outcomes of care in the context of a multifaceted intervention directed at general practitioners (GPs) encouraging regular follow-up and individualised goal-setting. DESIGN: A 6-year follow-up study. SETTING: A total of 243 Danish GPs and a population-based sample of 729 newly diagnosed, predominantly type 2 diabetic patients participated. MAIN OUTCOME MEASURES: Questionnaires and laboratory assessments were used to determine the proportion of patients reviewed regularly, and their pharmacological treatment and risk factors. RESULTS: During the study, the proportion of patients who had an annual clinical examination decreased from 100% to 77%. The proportion given oral anti-diabetic agents or insulin increased from 43% to 71%. Median glycated haemoglobin (HbA1c) dropped in the 2nd year to 7.7% (normal range 5.4-7.4%), after which it increased gradually, but remained on average at 1.3% above the upper limit of the normal range. Median blood pressure (systolic/diastolic), total cholesterols and fasting triglycerides were maintained at 145-150/81-85 mmHg, 6.0-6.2 mmol/l and 1.66-1.96 mmol/l, respectively. Initial weight loss was partly regained over 6 years. CONCLUSION: Among centrally supported GPs, most patients were regularly reviewed and obtained acceptable levels of risk factors for at least 6 years, although glycaemic control progressively deteriorated after an initial drop to near-normal average level.
We aimed to identify microRNAs (miRNAs) associated with type 2 diabetes and risk of developing the disease in skeletal muscle biopsies from phenotypically well-characterised twins.
We measured muscle miRNA levels in monozygotic (MZ) twins discordant for type 2 diabetes using arrays. Further investigations of selected miRNAs included target prediction, pathway analysis, silencing in cells and association analyses in a separate cohort of 164 non-diabetic MZ and dizygotic twins. The effects of elevated glucose and insulin levels on miRNA expression were examined, and the effect of low birthweight (LBW) was studied in rats.
We identified 20 miRNAs that were downregulated in MZ twins with diabetes compared with their non-diabetic co-twins. Differences for members of the miR-15 family (miR-15b and miR-16) were the most statistically significant, and these miRNAs were predicted to influence insulin signalling. Indeed, miR-15b and miR-16 levels were associated with levels of key insulin signalling proteins, miR-15b was associated with the insulin receptor in non-diabetic twins and knockdown of miR-15b/miR-16 in myocytes changed the levels of insulin signalling proteins. LBW in twins and undernutrition during pregnancy in rats were, in contrast to overt type 2 diabetes, associated with increased expression of miR-15b and/or miR-16. Elevated glucose and insulin suppressed miR-16 expression in vitro.
Type 2 diabetes is associated with non-genetic downregulation of several miRNAs in skeletal muscle including miR-15b and miR-16, potentially targeting insulin signalling. The paradoxical findings in twins with overt diabetes and twins at increased risk of the disease underscore the complexity of the regulation of muscle insulin signalling in glucose homeostasis.
The etiology of type 2 diabetes is multifactorial, including genetic as well as pre- and postnatal factors that influence several different defects of glucose homeostasis, primarily in muscle, beta-cells, and liver. In the present twin study, we report heritability estimates (h(2)) for measures of insulin secretion, insulin resistance, hepatic glucose production (HGP), and intracellular glucose partitioning using gold standard methods (euglycemic-hyperinsulinemic clamp technique, tritiated glucose infusion, indirect calorimetry, and intravenous glucose tolerance testing) among 110 younger (22-31 years of age) and 86 older (57-66 years of age) twins. To obtain a valid estimate of beta-cell function, insulin secretion was adjusted for the individual degree of insulin action (disposition index). In both age-groups there was a major genetic component in the etiology of insulin secretion that was statistically significantly higher among older twins (young h(2) = 0.75 [0.55-0.86] and old h(2) = 0.84 [0.69-0.92], P
Infections are a major clinical challenge for type 2 diabetes patients, but little is known about the impact of glycemic control. We used Cox regression analyses to examine the association between baseline and time-varying hemoglobin A1c (HbA1c) values and development of community antiinfective-agent-treated and hospital-treated infections in 69,318 patients with type 2 diabetes diagnosed between 2000 and 2012 in Northern Denmark. Incidence rates were 394/1,000 patient-years for community-treated infections and 63/1,000 patient-years for hospital-treated infections. The adjusted hazard ratios for community-treated infection at an HbA1c level of =10.50%, as compared with 5.50%-
We aimed to investigate metabolic risk factors, insulin sensitivity and insulin secretion in adolescent offspring of mothers with type 1 diabetes compared with offspring of non-diabetic mothers.
During 1993-1999, pregnancies of women with type 1 diabetes in Denmark were prospectively reported to a central registry in the Danish Diabetes Association. Data included information on maternal demography, diabetes status and pregnancy outcome. We invited 746 eligible children from this cohort (index offspring) to a follow-up examination. Control offspring were identified through The Danish Central Office of Civil Registration and matched with respect to date of birth, sex and postal code. Anthropometric measurements and blood sampling for metabolic characterisation, including an oral glucose tolerance test, were performed.
We examined 278 index offspring (mean age 16.7 years; range 13.0-19.8 years) and 303 control offspring (mean age 16.8 years; range 13.5-20.4 years). Index offspring had higher BMI SD score (0.44: 95% CI 0.21, 0.66) compared with controls, after adjustments for pubertal development and maternal pre-pregnancy BMI. Furthermore, index offspring had a higher prevalence of components included in metabolic syndrome and prediabetes (impaired fasting glucose and/or impaired glucose tolerance), with reduced insulin sensitivity and relative insulin secretion deficiency, compared with controls. Maternal HbA1c levels in pregnancy were not directly associated with offspring metabolic outcomes.
Adolescent offspring of mothers with type 1 diabetes had a less favourable metabolic profile and higher frequency of prediabetes than the background population. Significant associations between these outcomes and maternal HbA1c levels in pregnancy could not be demonstrated.
To investigate whether the use of incretin-based drugs (GLP-1 receptor agonists and dipeptidyl peptidase 4 [DPP4] inhibitors) is associated with acute pancreatitis.
The study was a nationwide population-based case-control study using medical databases in Denmark. Participants were 12,868 patients with a first-time hospitalization for acute pancreatitis between 2005 and 2012 and a population of 128,680 matched control subjects. The main outcome measure was the odds ratio (OR) for acute pancreatitis associated with different antihyperglycemic drugs. We adjusted for history of gallstones, alcoholism, obesity, and other pancreatitis-associated comorbidities and medications.
A total of 89 pancreatitis patients (0.69%) and 684 control subjects (0.53%) were ever users of incretins. The crude OR for acute pancreatitis among incretin users was 1.36 (95% CI 1.08-1.69), while it was 1.44 (95% CI 1.34-1.54) among users of other antihyperglycemic drugs. After confounder adjustment, the risk of acute pancreatitis was not increased among incretin users (OR 0.95 [95% CI 0.75-1.21]), including DPP4 inhibitor users (OR 1.04 [95% CI 0.80-1.37]) or GLP-1 receptor agonist users (OR 0.82 [95% CI 0.54-1.23]), or among nonincretin antihyperglycemic drug users (OR 1.05 [95% CI 0.98-1.13]), compared with nonusers of any antihyperglycemic drugs. Findings were similar in current versus ever drug users and in patients with pancreatitis risk factors. The adjusted OR comparing incretin-based therapy with other antihyperglycemic therapy internally while also adjusting for diabetes duration and complications was 0.97 (95% CI 0.76-1.23).
Our findings suggest that the use of incretin-based drugs appears not to be associated with an increased risk of acute pancreatitis.
OBJECTIVE: To study the influence of zygosity on blood pressure and serum lipid concentrations among male and female twins. SETTING: Department of Endocrinology, Odense University Hospital, Denmark. PARTICIPANTS: A total of 125 monozygotic and 178 dizygotic twin pairs aged 55-74 years of age, ascertained from The Danish Twin Register. DESIGN : Population-based cross-sectional study. MAIN OUTCOME MEASURES: Blood pressure and serum lipid concentrations. RESULTs: The prevalence of hypertriglyceridemia and hypercholesterolemia were higher among monozygotic compared with dizygotic twins, whereas the prevalence of hypertension was similar. The level of triglycerides [0.28 (0.44) versus 0.18 (0.41), P = 0.01] and total cholesterol [1.82 (0.17) versus 1.78 (0.19), P = 0.03] were significantly higher in monozygotic compared with dizygotic twins. Systolic blood pressure was non-significantly higher among monozygotic twins (136.8 (21.3) versus 134.1 (19.6), P = 0.10). When comparing monozygotic and dizygotic twins within each sex group, the difference in triglyceride level was only apparent among male twins and the differences in systolic blood pressure and total cholesterol were only seen among female twins. Birth weight as determined in a subgroup of the population was similar in monozygotic and dizygotic twins. CONCLUSIONS: Zygosity status per se influences fasting serum triglycerides and total-cholesterol and to some extent systolic blood pressure in twins, supporting an influence of an intrauterine component on lipid profiles. The influence is independent of birth weight and seems to be sex-specific.