Bendix Carstensen

The Danish National Diabetes Register: trends in incidence, prevalence and mortality

Aims/hypothesisThe aim of the study was to describe trends in the incidence rate, prevalence and mortality rate for diabetes in Denmark.MethodsHealthcare registers at the National Board of Health were used to compile a register of diabetic patients in the Danish population (5.4 million people). Age- and sex-specific prevalence, incidence rates, mortality rates and standardised mortality ratios relative to the non-diabetic part of the population were calculated.ResultsThe register contains records for about 360,000 persons with diabetes; 230,000 were alive at 1 January 2007, corresponding to an overall prevalence of 4.2%. The prevalence increased by 6% per year. In 2004 the incidence rates were 1.8 per 100,000 at age 40 years and 10.0 per 100,000 at age 70 years. The incidence rate increased 5% per year before 2004 and then stabilised. The mortality rate in the diabetic population decreased 4% per year, compared with 2% per year in the non-diabetic part of the population. The mortality rate decreased 40% during the first 3 years after inclusion in the register. The standardised mortality ratio decreased with age, from 4.0 at age 50 years to 2.5 at age 70 years and just under 2 at age 85 years, identically for men and women. The standardised mortality ratio decreased 1% per calendar year. The lifetime risk of diabetes was 30%.Conclusions/interpretationThe prevalence of diabetes in Denmark rose in 1995–2006, but the mortality rate in diabetic patients decreased faster than that of the non-diabetic population. The mortality rate decreased markedly just after inclusion in the register. Incidence rates have shown a tendency to decrease during the last few years, but this finding should be viewed with caution.

Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene in relation to insulin sensitivity among glucose tolerant Caucasians

Abstract.Aims/hypothesis: We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) diabetes mellitus among Scandinavian Caucasians. Methods: The Pro12Ala polymorphism was examined using PCR-RFLP. Whole-body insulin sensitivity measured under hyperinsulinaemic-euglycaemic conditions was estimated in a population-based sample of 616 glucose tolerant Swedish Caucasian men at age 70. In addition, insulin sensitivity index was measured using IVGTT and Bergman minimal modelling in a population-based sample of 364 young healthy Danish Caucasians. Finally, we evaluated whether the polymorphism predicted Type II diabetes and IGT in 841 seventy-year-old Swedish men. A case-control study was carried out in 654 unrelated Danish Type II diabetic patients and 742 Danish glucose tolerant subjects matched for age and sex. Results: Whole-body insulin sensitivity was significantly improved in carriers compared with non-carriers of the Ala-allele of the codon 12 polymorphism in Swedish Caucasian men (6.0 ± 2.5 vs 5.6 ± 2.5 mg · kg–1· min–1· [mU/l]–1· 100, p = 0.044). The same tendency, but not significant, was observed in the insulin sensitivity index among the group of young healthy Danish Caucasians. The incidence of Type II diabetes and IGT among the Swedish subjects at the age of 70 was similar in the three genotype-groups of the Pro12Ala variant and the Ala-allele was not related to a lower prevalence of Type II diabetes in Danish Caucasians. Conclusion/interpretation: The Ala-allele of the PPAR-γ2 polymorphism is associated with improved whole body insulin sensitivity among Swedish Caucasians. [Diabetologia (2001) 44: 1170–1176]

The National Diabetes Register

Introduction: A National Diabetes Register was established in the National Board of Health in 2006 following a pilot study showing the feasibility of doing so based on existing registers. Content: The register contains data of birth, date of inclusion, and date of death as well as information on the criteria met for inclusion. Validity and coverage: The register is more than 90% complete when compared to records of general practitioners, and it covers the entire Danish population. Conclusion: The register is a source of demographic information for the diabetes population in itself, but also a source of linkable information for studies of diabetes as outcome and as determinant.

Statistical Models for Assessing Agreement in Method Comparison Studies with Replicate Measurements

Method comparison studies are usually analyzed by computing limits of agreement. It is recommended that replicate measurements be taken by each method, but the resulting data are more cumbersome to analyze. We discuss the statistical model underlying the classical limits of agreement and extend it to the case with replicate measurements. As the required code to fit the models is non-trivial, we provide example computer code to fit the models, and show how to use the output to derive measures of repeatability and limits of agreement.

Genetic Variation in the Renin-Angiotensin System and Progression of Diabetic Nephropathy

The impact of polymorphisms in the genes coding for angiotensinogen (M235T), ACE (ID), and angiotensin II type 1 receptor (A(1166)-->C) on decline in GFR and doubling of s-creatinine or development of ESRD in patients with type 1 diabetes and diabetic nephropathy (DN) was tested. From 1985, all patients (n = 169) who had established diabetic nephropathy and were treated with angiotensin-converting enzyme inhibition (ACE-I) were identified consecutively at Steno Diabetes Center. Patients were followed for a median of 6 yr (range, 3 to 15 yr), with nine (range, three to 29) measurements of GFR ((51)Cr-EDTA). In a Cox proportional hazards model corrected for other risk factors, the D allele (ACE/ID) was associated with time to doubling of s-creatinine/ESRD (rate ratio, 1.81 per allele; 95% confidence interval, 1.09 to 3.03; P = 0.02). A new interaction hypothesis was generated demonstrating that the following variables were associated with accelerated decline in GFR: albuminuria (estimate, 2.12 ml/min per yr per 10-fold increase in albuminuria; P < 0.001), mean BP (estimate, 0.88 ml/min per yr per 10 mmHg; P = 0.02), hemoglobin A(1c) (estimate, 0.54 min/min per yr per 1%; P = 0.02), and number of M (M235T)/D (ID)/A (A(1166)-->C) alleles (estimate, 0.45 ml/min per yr per allele; P = 0.049). Number of M/D/A alleles also influenced time to doubling of s-creatinine or ESRD. In this study of patients with type 1 diabetes, the D allele of the ACE/ID polymorphism in addition to nongenetic risk factors independently accelerated progression of DN during ACE-I. Interaction between polymorphisms in the renin-angiotensin system also influenced the loss of kidney function. This new genetic interaction model needs to be confirmed in future studies.

Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes : a cross-sectional survey

Aims  The reported risk of severe hypoglycaemia in insulin‐treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects with insulin‐treated Type 2 diabetes receiving currently recommended multifactorial intervention.

Comparability of venous and capillary glucose measurements in blood

Aim  Diabetes and glucose intolerance are diagnosed by measurement of glucose in blood. Glucose is usually measured as venous plasma or capillary whole blood and diagnostic criteria frequently provide equivalence estimates for these two methods. This study examined the relationship between glucose measured in capillary and venous samples collected at random, fasting and 2 h after oral glucose.

Long‐term trends in the incidence of type 1 diabetes in Denmark: the seasonal variation changes over time

There is a worldwide increase of type 1 diabetes mellitus (T1DM). In 1996, the Danish population‐based registry was initiated including all newly diagnosed children aged 0–15 yr. This is the report of incidence and seasonal variation for the first 10 yr of the registry. The data was analyzed using Poisson’s regression analysis. A total of 2166 children with diabetes were diagnosed before the age of 15 yr between 1996 and 2005. In this period, the annual increase in childhood T1DM was 3.43% (95% confidence interval: 1.91–4.97), which was unaffected by age and gender. Seasonal variation in incidence rates varied by year but not by age and gender. In conclusion, there is a steep increase in incidence of childhood T1DM in Denmark; the increase is comparable with the increase seen in other European countries. There is a significant seasonal variation that changes on a year‐to‐year basis. The observed variations in cadence rates may be associated with viral epidemics, sunshine exposure, or vitamin D levels and suggest further exploration of these relations.

Associations Between Features of Glucose Exposure and A1C The A1C-Derived Average Glucose (ADAG) Study

OBJECTIVE Various methods are used to quantify postprandial glycemia or glucose variability, but few have been compared and none are standardized. Our objective was to examine the relationship among common indexes of postprandial glycemia, overall hyperglycemia, glucose variability, and A1C using detailed glucose measures obtained during everyday life and to study which blood glucose values of the day provide the strongest prediction of A1C. RESEARCH DESIGN AND METHODS In the A1C-Derived Average Glucose (ADAG) study, glucose levels were monitored in 507 participants (268 type 1 diabetic, 159 type 2 diabetic, and 80 nondiabetic subjects) with continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SMBG) during 16 weeks. We calculated several indexes of glycemia and analyzed their intercorrelations. The association between glucose measurements at different times of the day (pre- and postprandial) and A1C was examined using multiple linear regression. RESULTS Indexes of glucose variability showed strong intercorrelation. Among postprandial indexes, the area under the glucose curve calculated from CGM 2 h after a meal correlated well with the 90-min SMBG postprandial measurements. Fasting blood glucose (FBG) levels were only moderately correlated with indexes of hyperglycemia and average or postprandial glucose levels. Indexes derived with SMBG strongly correlated with those from CGM. Some SMBG time points had a stronger association with A1C than others. Overall, preprandial glucose values had a stronger association with A1C than postprandial values for both diabetes types, particularly for type 2 diabetes. CONCLUSIONS Indexes of glucose variability and average and postprandial glycemia intercorrelate strongly within each category. Variability indexes are weakly correlated with the other categories, indicating that these measures convey different information. FBG is not a clear indicator of general glycemia. Preprandial glucose values have a larger impact on A1C levels than postprandial values.

Increased Risk of Type 2 Diabetes in Elderly Twins

OBJECTIVE Genetic susceptibility, low birth weight (LBW), and aging are key etiological factors in the development of type 2 diabetes. LBW is common among twins. It is unknown whether twin status per se is associated with risk of type 2 diabetes, and valid concordance rates of type 2 diabetes in twins on a lifetime perspective are lacking. RESEARCH DESIGN AND METHODS A clinical study was done on a population-based cohort of same-sex elderly monozygotic (MZ) and dizygotic (DZ) twins (n = 297) and singleton control subjects (C) (n = 71) including measures of anthropometry and glucose tolerance. In addition, type 2 diabetes incidence cases in twins (n = 626) and singletons (n = 553) were identified through the National Diabetes Register. RESULTS Twins were more abdominally obese, insulin resistant, and glucose intolerant, as evidenced by a higher A1C (%) (means ± SD) (MZ: 6.0 ± 1.0, DZ: 5.8 ± 0.7, C: 5.6 ± 0.3, P = 0.004) and 120-min post–oral glucose tolerance test plasma glucose levels (in mmol/l) (MZ: 8.6 ± 4.6, DZ: 8.4 ± 3.9, C: 6.8 ± 2.4, P = 0.003) compared with singletons. Importantly, twins had a higher prevalence of type 2 diabetes (MZ: 17.5% [95% CI 14.4–20.6], DZ: 15.7% [13.1–18.3], C: 5.6% [3.0–8.2], P = 0.03) together with a 60% higher incidence rate of type 2 diabetes compared with singletons. Cumulative concordance rates of type 2 diabetes to the age of 84 years were similar among elderly MZ (0.76 [0.68–0.84]) and DZ (0.71 [0.63–0.78]) twins. CONCLUSIONS Twin status per se is associated with abdominal obesity, insulin resistance, and increased prevalence of type 2 diabetes in elderly twins. The data support a quantitatively significant impact of the fetal environment as opposed to genetics on risk of type 2 diabetes.