To assess the dietary supplement use in adult individuals with type 1 diabetes, and to study the association between vitamin D supplementation and glycaemic control in an observational ...cross-sectional study.
The study subjects were participants of the Finnish Diabetic Nephropathy Study. Data were included from all individuals with type 1 diabetes with estimated glomerular filtration rate ≥60 mL/min/1.73 m
, who had completed a diet questionnaire. In the questionnaire, the participants reported dietary supplement use for the past 30 days. A thorough investigation with an assessment of the blood panel was conducted at the study visit.
Data were available from 1181 individuals (43% men, mean ± SD age 45 ± 13 years). Altogether 62% of the sample reported supplement use; 56% reported some vitamin or mineral and 27% reported non-vitamin and non-mineral supplement use. Supplement use was more frequent among women and those supplementing had better overall health. In the study sample, of the vitamins and minerals, vitamin D (45%) and magnesium (31%), respectively, were the most frequently reported. In the multivariable models, vitamin D supplementation was associated with better glycaemic control. Starting from a daily dose of ≥30 μg, there was evidence of improving glycaemic control with higher doses of supplemental vitamin D (e.g., for 30 μg: B Wald Confidence Internal, p-value, -2.76 -5.03 to -0.49, 0.017).
Supplement use was frequent in this sample of adult individuals with type 1 diabetes. Due to potential drug-supplement interactions, the attending physicians should be aware of their patients' supplement use. The causality between vitamin D supplementation and glycaemic control should be assessed in a randomized controlled trial.
The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The ...Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.
Aims
The MARLINA‐T2D study (ClinicalTrials.gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard‐of‐care in individuals with type 2 diabetes ...and albuminuria.
Methods
A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48–86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and urinary albumin‐to‐creatinine ratio (UACR) 30–3000 mg/g despite single agent renin‐angiotensin‐system blockade were randomized to double‐blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time‐weighted average of percentage change from baseline in UACR over 24 weeks, respectively.
Results
Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% ± 0.9% (62.2 ± 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo‐adjusted mean change in HbA1c from baseline was −0.60% (−6.6 mmol/mol) (95% confidence interval CI, −0.78 to −0.43 −8.5 to −4.7 mmol/mol; P < .0001). The placebo‐adjusted gMean for time‐weighted average of percentage change in UACR from baseline was −6.0% (95% CI, −15.0 to 3.0; P = .1954). The adverse‐event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups.
Conclusions
In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo‐adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.
Aims
To determine the effect of different stages of diabetic nephropathy (DN) and sex on the excess and absolute morbidity of coronary artery disease (CAD) and stroke in people with type 1 diabetes ...(T1D) in order to distinguish different cardiovascular disease (CVD) risk profiles in people with T1D.
Materials and Methods
The study included 4410 people with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), divided by DN status, and a control population of 12 434 people without diabetes. CVD events were identified from the Finnish nationwide health registries. Cumulative incidences for CAD and stroke were calculated and standardized incidence ratios (SIRs) were estimated between participants with T1D and the control group, stratified by DN status and sex.
Results
There were 487 incident CADs and 290 strokes at the end of 2014 (median follow‐up 12.9 years). The cumulative incidence rates of CAD and stroke were similar in men and women within different nephropathy groups. The SIR for CAD was 7.5 (95% confidence interval CI 6.9‐8.2), 17.2 (95% CI 14.9‐19.5) in women and 5.3 (95% CI 4.7‐5.9) in men. The women‐to‐men ratio of SIR increased by nephropathy group: 3.3, 3.7, 5.3 and 6.8 in the normo‐, micro‐ and macroalbuminuria and end‐stage renal disease (ESRD) groups, respectively. The SIR for stroke was 5.0 (95% CI 4.3‐5.5), similar in men and women. The women‐to‐men ratio of SIR for stroke was 0.8, 1.3, 1.6 and 1.7, in the normo‐, micro‐ and macroalbuminuria and ESRD groups, respectively. The SIR in participants with normoalbuminuria and an estimated glomerular filtration rate ≥90 mL/min/1.73 m2 was 3.5 (95% CI 2.5‐4.5) for CAD and 1.6 (95% CI 1.0‐2.3) for stroke.
Conclusions
Although the excess CVD risk is several‐fold greater in women compared to men, the absolute CVD risk in men and women was equal when nephropathy was taken into account. Even participants with normoalbuminuria and normal kidney function were found to have an excess CVD risk compared with the control group without diabetes.
Aims/hypothesis
Lipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in ...humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes.
Methods
Individuals (
n
= 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria.
Results
During a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median IQR for eGFR change: <−4.4 −6.8, −3.1 ml min
−1
1.73 m
−2
year
−1
), even after adjustment for classical lipid variables such as HDL-cholesterol and triacylglycerols (OR 95% CI: 1.36 1.15, 1.61,
p
< 0.001). Similarly, sphingomyelin increased the risk of progression to ESRD (HR 95% CI: 1.53 1.19, 1.97,
p
= 0.001). Moreover, sphingomyelin increased the risk of CHD (HR 95% CI: 1.24 1.01, 1.52,
p
= 0.038). However, sphingomyelin did not perform better than albuminuria in the prediction of eGFR decline.
Conclusions/interpretation
This study demonstrates for the first time in a prospective setting that sphingomyelin is associated with the fastest eGFR decline and progression to ESRD in type 1 diabetes. In addition, sphingomyelin is a risk factor for CHD. These data suggest that high sphingomyelin level, independently of classical lipid risk factors, may contribute not only to the initiation and progression of kidney disease but also to CHD.
Graphical abstract
Diabetic kidney disease and other long-term complications are common in diabetes, and comprise the main cause of co-morbidity and premature mortality in individuals with diabetes. While familial ...clustering and heritability have been reported for all diabetic complications, the genetic background and the molecular mechanisms remain poorly understood. In recent years, genome-wide association studies have identified a few susceptibility loci for the renal complications as well as for diabetic retinopathy, diabetic cardiovascular disease and mortality. As for many complex diseases, the genetic factors increase the risk of complications in concert with the environment, and certain associations seem specific for particular conditions, for example, SP3-CDCA7 associated with end-stage renal disease only in women, or MGMT and variants on chromosome 5q13 associated with cardiovascular mortality only under tight glycaemic control. The characterization of the phenotypes is one of the main challenges for genetic research on diabetic complications, in addition to an urgent need to increase the number of individuals with diabetes with high quality phenotypic data to be included in future genetic studies.
Incidence of Type 1 Diabetes in Finland Harjutsalo, Valma; Sund, Reijo; Knip, Mikael ...
JAMA : the journal of the American Medical Association,
07/2013, Letnik:
310, Številka:
4
Journal Article
Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD ...development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders.
Aims/hypothesis
The aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes.
Methods
The study ...included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up.
Results
One pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 95% CI 1.15, 1.84), after adjustment for age, sex, HbA
1c
, hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data.
Conclusions/interpretation
There is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.
Data from three completed cardiovascular outcome trials (CVOTs), EMPA‐REG OUTCOME, CANVAS Program and DECLARE‐TIMI 58, add to the evidence supporting the potential renoprotective effects of ...sodium‐glucose linked transporter‐2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient‐relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end‐stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal‐specific elements of this primary endpoint (P <0.001). Canagliflozin has therefore become the first US‐approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient‐relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported.
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