Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study.

OBJECTIVE: To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS: Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56-2.00]; type 2 diabetes, 1.64 [95% CI 1.55-1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50-2.11]; type 2 diabetes, 1.85 [95% CI 1.64-2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year. CONCLUSIONS: SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.

Design and methodology of the PRIMETIME 1 cohort study: PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy.

Background: Clinical features of diabetic kidney disease alone cannot differentiate between the histopathology that defines diabetic nephropathy (DN) and non-diabetic nephropathy (NDN). A kidney biopsy is necessary to make the definitive diagnosis of DN. However, there is no consensus on when to perform a kidney biopsy in individuals with diabetes and kidney disease. Furthermore, the implications of NDN versus DN for management, morbidity and kidney prognosis are unclear. To address the gap in knowledge, we aimed to create a national retrospective cohort of people with diabetes and a performed kidney biopsy. Methods: Adults diagnosed with diabetes in Denmark between 1996 and 2020 who had a kidney biopsy performed were included. The cohort was established by linking a nationwide diabetes registry with the Danish Pathology Registry. Data from 11 national registries and databases were compiled. The type of kidney disease was classified using a three-step analysis of Systematized Nomenclature of Medicine codes reported in relation to the histopathological examinations of kidney tissue. The final cohort and classification of kidney disease was as follows: out of 485 989 individuals with diabetes 2586 were included, 2259 of whom had type 2 diabetes. We were able to classify 599 (26.5%) with DN, 703 (31.1%) with NDN and 165 (7.3%) with mixed disease in individuals with type 2 diabetes. In individuals with type 1 diabetes, 132 (40.4%) had DN, 73 (22.3%) NDN and 39 (11.9%) mixed disease. The remaining could not be classified or had normal histology. The overall median (Q1-Q3) follow-up time was 3.8 (1.6-7.2) years. Conclusions: This cohort is a novel platform based on high-quality registry data for important longitudinal studies of the impact of kidney disease diagnosis on prognosis. With regular updates of data from the Danish registries, the presented follow-up will increase over time and is only limited by emigration or death.

Christmas article: Snacking preferences at the office during the Christmas season ­ a secret intervention study among diabetes researchers.

Introduction To quantify the effect of Christmas vs. New Year's resolutions season on snacking preferences by measuring intake of four different snacks. Methods Prospective ad libitum intervention snacking study with four combinations of sweet/savory and fatty/non-fatty snacks: cookies, candy, TUC crackers, and rye crackers. A snacking buffet, continuously refilled by a secret Santa, was provided during the Christmas season and New Year's Resolutions season by the secret Santas of the office. Participants were diabetes researchers and were not informed about the study before the end of data collection. The main outcome was daily intake (g) of the four snacks. Results In general, the intake of candy was high compared to the other snacks. The average intake of cookies was significantly higher during the Christmas season compared to New Year's resolution season (8 g/day/participant, p = 0.03), but decreased when approaching Christmas and increased again as time passed by after Christmas (although not significantly). The strongest correlation between the intake of snacks was found between the two sweet snacks, i.e., candy and cookies. Conclusion Researchers have a high preference for sweet foods, especially candy. Irrespective of the type of snack, the preference for cookies was high during the Christmas season but seemed to decrease with decreasing proximity to Christmas, hence, canceling Christmas will unlikely improve diet quality. In fact, we encourage further research to consider whether having Christmas all year could be a potential prevention strategy in the combat of the obesity pandemic. Funding none. Trial registration none.

Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to compare the performance of the second-generation basal insulins, insulin degludec 100 U/ml (Deg-100) and insulin glargine 300 U/ml (Gla-300), in terms of change in HbA1c, hospitalisation for hypoglycaemia and all-cause mortality among individuals with type 2 diabetes and concurrent chronic kidney disease. METHODS: This register-based cohort study, based on the entire Danish diabetes population, included 6519 new users of Deg-100 and Gla-300 with type 2 diabetes and moderate to end-stage chronic kidney disease. HbA1c trajectories, from initiation of either Deg-100 (2013) or Gla-300 (2015) to end of follow-up (2020), were modelled with mixed-effect models while rates of hospitalisation for hypoglycaemia and all-cause mortality were modelled in separate models using Poisson likelihood. RESULTS: Of the 6519 (44% women) individuals included in the study, 3747 were exposed to Deg-100 and 2772 to Gla-300. Both mean (SD) type 2 diabetes duration (14.4 [6.6] years vs 15.2 [6.7] years) and median (IQR) chronic kidney disease duration (2.3 [1.3, 3.9] years vs 2.8 [1.6, 4.6] years) were significantly shorter in the Gla-300 group. The median (IQR) follow-up time was similar between groups: 1.0 (0.5-1.6) year for Gla-300 and 1.0 (0.3-1.5) year for Deg-100. In both groups mean HbA1c levels were reduced by 13-14 mmol/mol (1.2-1.3%) from initiation to end of follow-up, with the largest reduction (of 8-9 mmol/mol [0.7-0.8%]) occurring during the first year. There was no significant difference in HbA1c reduction between Deg-100 and Gla-300. Both the rate of hospitalisation for hypoglycaemia (rate ratio 1.02 [95% CI 0.70, 1.49], Deg-100 vs Gla-300) and the rate of all-cause mortality (rate ratio 0.98 [95% CI 0.84, 1.15], Deg-100 vs Gla-300) were similar between the groups. CONCLUSIONS/INTERPRETATION: We found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.

Severe Mental Illness and the Risk of Diabetes Complications: A Nationwide, Register-based Cohort Study.

CONTEXT: Individuals with severe mental illness (SMI) are at increased risk of developing type 2 diabetes. OBJECTIVE: This work explores whether individuals with diabetes and SMI are also at increased risk of diabetes complications and the potential age-specific differences in development of these. METHODS: Using nationwide registry data, we followed the entire Danish population with type 2 diabetes from January 1, 1996 to December 31, 2018. Exposure was SMI (schizophrenia, bipolar, or depression disorders). Outcome was diabetes complications (nephropathy, retinopathy, lower limp amputations, and cardiovascular disease). We applied Poisson regression models to estimate overall incidence rate ratios (IRRs) and age-specific incidence rates (IRs) and IRRs of the first event of each complication in individuals with SMI compared to individuals without SMI. The models were adjusted for sex, age, diabetes duration, calendar year, education, and migration status. RESULTS: We followed 371 625 individuals with type 2 diabetes, of whom 30 102 had coexisting diagnosed SMI. Individuals with SMI had a higher IR of nephropathy (IRR: 1.15; 95% CI, 1.12-1.18), amputations (IRR: 1.15; 95% CI, 1.04-1.28), and cardiovascular disease (men: IRR: 1.10; 95% CI, 1.05-1.15, women: IRR: 1.18; 95% CI, 1.13-1.22) but a lower IR of retinopathy (IRR: 0.75; 95% CI, 0.70-0.81) when compared to individuals without SMI, after adjustment for confounders. For all complications except amputations, the difference in IR was highest in the younger age groups. CONCLUSION: Individuals with type 2 diabetes and SMI had a higher risk and an earlier onset of several diabetes complications diagnoses, emphasizing focusing on improving diabetes management in younger age groups with SMI.

Discontinuation of diabetes medication in the 10 years before death in Denmark: a register-based study.

BACKGROUND: Discontinuation of diabetes medication in the last years of life has been suggested to improve quality of life while deemed safe to implement. However, the extent, patterns, and secular changes in discontinuation of glucose-lowering medication in older people with type 2 diabetes have been scarcely described. We therefore aimed to describe the trends in the use of glucose-lowering medication during the last 10 years of life of older people and explore how key clinical and socioeconomic covariates are associated with these patterns. METHODS: In this register-based cohort study, all individuals with type 2 diabetes who died aged 80 years or older between Jan 1, 2006, and Dec 31, 2018, were identified through the Danish Diabetes Register and linked to the Danish National Prescription Registry. We followed the population backwards in time from death to date of last medication intake. To estimate the cumulative proportion of people on glucose-lowering medication, a Poisson regression model for the rate of medication as a function of time before death (0 to 10 years before death) and calendar year of death (2006-18) was fitted. Both single-substance and combination glucose-lowering medications were included and categorised as insulins, sulfonylureas, metformin, DPP-4 inhibitors, GLP-1 analogues, SGLT2 inhibitors, acarbose, and thiazolidinediones. Insulin was further subdivided into four groups: fast-acting, intermediate-acting, long-acting, and mixed insulin. To identify which covariates were associated with discontinuation, estimates were adjusted for sex, age at death, diabetes duration at time of death, the total number of diabetes complications at time of death (from no complications to four or more), level of education, immigrant status, and income quartile. FINDINGS: 52 523 individuals (28 746 [54·7%] females and 23 777 [45·3%] males) were identified, with a mean age at type 2 diabetes diagnosis of 77 years (SD 8), median age at death of 86 years (IQR 83-90), and median diabetes duration at death of 9 years (IQR 5-14). We found a considerable discontinuation of glucose-lowering medication during the last 10 years of life, with the proportion of people on glucose-lowering medication starting at between 89% (95% CI 87-91) in 2006 and 87% (86-88) in 2018 at 10 years before death and decreasing to between 52% (50-54) in 2006 and 38% (37-39) in 2018 at the time of death. Specifically, we found that the proportion of people on sulfonylureas, at any time before death, decreased substantially from 2006 to 2018, whereas the proportion on metformin and DPP-4 inhibitors increased with calendar year of death. Changes were less pronounced for the remaining medications. The overall discontinuation patterns changed with increasing calendar year of death, such that discontinuation rates increased and occurred earlier (further away from time of death) with increasing calendar year. Discontinuations were generally more pronounced during the last year of life. Proportions of people on medication and patterns of discontinuation, as well as the association with covariates, varied with medication class. Covariates most frequently associated with changes in discontinuation rates were sex, age at death, type 2 diabetes duration at death, and number of complications. For example, females were less likely to receive metformin than males at all years before death (rate ratio 0·91 (95% CI 0·89-0·94, p<0·0001), and there was a negative association between the proportion of individuals on metformin and increasing age at death (rate ratio per year increase 0·96 [0·96-0·96], p<0·0001) and type 2 diabetes duration (0·95 per year increase [0·94-0·95], p<0·0001). INTERPRETATION: Our results suggest that increased focus on and implementation of discontinuation of glucose-lowering medication in recent years might have had an effect on discontinuation patterns, particularly during the last year of life. FUNDING: None.