Glycemic Control and Excess Cardiovascular Mortality in Type 1 Diabetes

Teleb, Mohamed; Switzer, Maryna Popp; Elhanafi, Sherif; Elfar, Ahmed; Juan, Zinnia T. San

doi:10.1007/s11886-016-0700-6

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…However, it should be noted that, in our study individuals with any given complication could have subclinical levels of other complications. Other studies have found an association between proliferative retinopathy and mortality risk [29,30]. An even stricter definition of retinopathy might have enabled us to support these findings; however, such detailed information was not available in the dataset at hand.…”

Section: Discussionmentioning

confidence: 73%

Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study

et al. 2019

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Aims/hypothesis The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications. Methods This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden. Results During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA 1c , LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years. Conclusions/interpretation Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.

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Section: Discussionmentioning

confidence: 73%

Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study

et al. 2019

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“…However, the fact that the hypertrophic cardiomyopathy and left ventricular dysfunction in a mouse model of lipodystrophy were ameliorated by lowering blood glucose levels (11) suggests hyperglycemia may contribute to impaired cardiac function in diabetes. Furthermore, nonobese patients with diabetes (including type 1 or monogenic diabetes) may also develop cardiac complications (12,13), supporting the idea that hyperglycemia alone is sufficient to cause cardiac disease. Likewise, in a large study of individuals with type 2 diabetes (T2D), a 1% increase in HbA 1c was associated with an increased risk of heart failure, independent of obesity, suggesting hyperglycemia is an independent risk factor for cardiac dysfunction (14).…”

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confidence: 87%

Cardiac Dysfunction and Metabolic Inflexibility in a Mouse Model of Diabetes Without Dyslipidemia

et al. 2018

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Diabetes is a well-established risk factor for heart disease, leading to impaired cardiac function and a metabolic switch toward fatty acid usage. In this study, we investigated if hyperglycemia/hypoinsulinemia in the absence of dyslipidemia is sufficient to drive these changes and if they can be reversed by restoring euglycemia. Using the βV59M mouse model, in which diabetes can be rapidly induced and reversed, we show that stroke volume and cardiac output were reduced within 2 weeks of diabetes induction. Flux through pyruvate dehydrogenase was decreased, as measured in vivo by hyperpolarized [1-C]pyruvate MRS. Metabolomics showed accumulation of pyruvate, lactate, alanine, tricarboxyclic acid cycle metabolites, and branched-chain amino acids. Myristic and palmitoleic acid were decreased. Proteomics revealed proteins involved in fatty acid metabolism were increased, whereas those involved in glucose metabolism decreased. Western blotting showed enhanced pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) expression. Elevated PDK4 and UCP3 and reduced pyruvate usage were present 24 h after diabetes induction. The observed effects were independent of dyslipidemia, as mice showed no evidence of elevated serum triglycerides or lipid accumulation in peripheral organs (including the heart). The effects of diabetes were reversible, as glibenclamide therapy restored euglycemia, cardiac metabolism and function, and PDK4/UCP3 levels.

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