At the first hybrid annual meeting of the German Diabetes Association, this year everything revolved around the motto “Hand in hand to the goal – simple.better.measurable”. Around 7000 participants learned about the latest developments in research and treatment of the chronic metabolic disease. In recent years, basic research in particular has made it possible to improve the care of those affected.
To maintain essential functions, mitochondria form a dynamic network within the cell. This is subject to constant merger and division processes. The main mediator of mitochondrial division is dynamin-related protein (Drp1), which causes strangulation of fused mitochondria through its GTPase activity. However, excessive division processes lead to increased fragmentation of mitochondria. The involvement of this process in the pathogenesis of diabetes mellitus is discussed. Therefore, a study was conducted to further elucidate the consequences of altered Drp1 activity. For this, Drp1 activity was reduced using stable expression of the GTPase inactive Drp1 mutant K38A in MIN6 cells. Comparatively, MIN6 cells with stable Drp1 overexpression were then considered. Mitochondrial morphology was analyzed using MTGreen staining. It was observed that control cells showed a homogeneous network structure leading to increased elongation and formation of mitochondrial clusters after loss of function of Drp1. MIN6 cells with inactive Drp1 showed significantly higher membrane potential in comparison with the same expression of respiratory chain proteins. Mitophagy-associated respiratory chains linked and mitochondrial dynamics genes were increased in expression compared with control centers. The researchers concluded that a reduction in Drp1 activity in MIN6 cells leads to increased elongation and cluster formation of mitochondria. Increased expression of the protein results in fragmentation of the network. While overexpression of Drp1 leads to alteration of the respiratory chain, the increase in membrane potential, mitophagy, and mitochondrial dynamics in K38A cells suggests protective effects on the beta cell that may counteract the progression of type 2 diabetes.
Influence of hypercholesterolemia on type 1 diabetes
Another study analyzed the prevalence of cardiovascular (CV) risk factors in young people with type 1 diabetes (T1D) and the differences between patients with and without hypercholesterolemia. CV risk factors included hypercholesterolemia with an LDL-C ≥130 mg/dl, microalbuminuria (ACR 2.5-25 or 3.5-33 mg/mmol or AER 20-200 µg/min/1.73m2 KO), and arterial hypertension with RR >90. Cardiovascular, socidemographic, and lifestyle factors were queried. In addition, participants’ HbA1c, glucose levels in the target range (TIR), lipids, and albuminuria, as well as BMI-SDS, pubertal stage, insulin therapy, arterial blood pressure, and intima-media thickness (IMD) were recorded. Of 333 patients, hypercholesterolemia was detected in 30, albuminuria in 59, and arterial hypertension in 11. Hypercholesterolemia was associated with a family history of CV disease, low TIR, higher total insulin requirements, higher basal insulin requirements, higher triglyceride levels, higher total cholesterol levels, lower HDL levels, and higher systolic and diastolic blood pressure levels. Sex, pubertal status, duration of diabetes, type of therapy, and type of glucose monitoring did not differ between patients with and without LDL hypercholesterolemia. No association was also demonstrated between IMT and hypercholesterolemia. Accordingly, in young patients with type 1 diabetes and LDL hypercholesterolemia, family history, metabolic status, insulin requirements, and other CV risk factors should be considered in a focused manner, and specific counseling and treatment of this group should be initiated.
High burden on parents of children affected by type 1 diabetes
The treatment of type 1 diabetes involves many tasks and demands in everyday life. Especially with younger children, these are the responsibility of the parents. These challenges can lead to increased stress and overwhelm for parents, which can impact the quality of diabetes care provided to children. A multicenter, anonymous cross-sectional survey was therefore conducted to examine parental stress. In addition to socidemographic information and information regarding treatment, the extent of emotional, physical, and daily stress was assessed using a 5-point Likert scale. It was found that emotional stress was the highest compared to physical and daily stress. Mothers – and especially single mothers – reported the highest stress scores. The older the child, the lower the physical and daily stress became. Emotional stress, on the other hand, did not decrease. The use of new technologies also increased the daily and physical burden on parents. Unsurprisingly, 78% of parents wanted additional diabetes education.
The influence of chronic hyperglycemia on cardiomyopathy.
Diabetic cardiomyopathy is characterized by the loss of metabolic flexibility in the presence of an oversupply of each nutritional component. Due to decreased activity of metabolic pathways, the diabetic heart experiences energy depletion. High glucose levels slow down fatty acid oxidation, and high fatty acid concentrations inhibit glycolysis. To study these effects, a GLUT4-overexpressing cell line (H9C2KE2) was developed based on the H9C2 cell line. This shows essential characteristics of diabetic cardiomyopathy in hyperglycemia. Stably GLUT4-overexpressed rat cardiomyoblast cells were cultured under normal cell-type glucose levels and hyperglycemic conditions. Expression profiles of selected proteins were comparatively analyzed. Hyperglycemia and increased glucose influx were shown to result in altered substrate fluxes in metabolism. Increased glucose uptake causes pyruvate levels and subsequently L-lactate levels to rise. In the citrate cycle, downregulation of fumarase leads to fumarate accumulation, which is the cause of oxidative stress and disrupts the further course of the citrate cycle. Thus, ATP yield in oxidative phosphorylation is lowered, resulting in energy depletion. This in turn leads to structural damage to the myocardium, measured as BNP increase. All in all, chronic hyperglycemia in H9C2KE2 is associated with significant BNP increase, oxidative stress, and apoptosis. The negative impact of glucose overload on the citrate cycle with decreased energy yield represents a new approach in understanding metabolic cardiomyopathy.
Insulin action in the brain decreases with age
Insulin action in the brain plays an important role in the regulation of glucose metabolism and in cognitive processes. However, patients with obesity and type 2 diabetes show impaired insulin action in the brain. The extent to which age and peripheral insulin sensitivity affect the action of insulin in the brain was investigated using functional magnetic resonance imaging (fMRI) data [3]. On two measurement dates, 110 subjects between the ages of 21 and 74 underwent fMRI – before and after taking intranasal insulin or placebo. Insulin action in the hippocampus showed a significant negative relationship with age. The older the subjects were, the less they responded to the centrally acting insulin. This relationship was more pronounced in women than in men. In contrast, insulin action in the amygdala, hypothalamus, insula, and caudate nucleus showed no correlation. In the insular cortex, however, an interaction effect was observed in younger subjects. These showed stronger central insulin action with higher peripheral insulin sensitivity.
Diabetic polyneuropathy in focus
Diabetic polyneuropathy is a significant complication of diabetes mellitus. It occurs in approximately 20-30% of affected individuals. The aim of one study was to characterize the peripheral nerves of patients with Ty-2 diabetes using nerve ultrasound, as results in recent years have been inconsistent regarding nerve enlargements. For this purpose, 80 patients with type 2 diabetes were studied. Anamnestic data, laboratory values, medication, neurological examinations, scores, electroneurography and nerve sonography were recorded. Nerve ultrasound showed few sites of nerve enlargement at noncompression sites. However, it could be confirmed that the cross-sectional areas at the compression points are enlarged. These were improved after one year in two of 23 follow-up patients after dietary changes, weight reduction of approximately 6%, and medication changes. The improvements suggest that changes may be directly visible with nerve ultrasound. Diabetic polyneuropathy cannot be reliably detected with the UPS score. However, the score is useful for ruling out competing inflammatory demyelinating causes of neuropathy.
Congress: 56th Annual Meeting of the German Diabetes Society (DDG)
CARDIOVASC 2022; 21(2): 26-27
