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Objective: To study potential risk factors for retinopathy in diabetic and nondiabetic individuals.Research Design and Methods: The Hoorn Study is a population-based study including 2,484 50- to 74-year-old Caucasians. A subsample of 626 individuals stratified by age, sex, and glucose tolerance underwent extensive measurements during 1989-1992, including ophthalmologic examination and two-field 45-degree fundus photography. The prevalence of (diabetic) retinopathy was assessed among individuals with normal glucose metabolism (NGM) and impaired glucose metabolism (IGM) and individuals with newly diagnosed diabetes mellitus (NDM) and known diabetes mellitus (KDM) (new World Health Organization 1999 criteria).Results: The prevalence of retinopathy was 9% in NGM, 11% in IGM, 13% in NDM, and 34% in KDM. Retinopathy worse than minimal nonproliferative diabetic retinopathy was present in 8% in KDM and 0-2% in other glucose categories. The prevalence of retinopathy was positively associated with elevated blood pressure, BMI, cholesterol, and triglyceride serum levels in all glucose categories. The age-, sex-, and glucose metabolism category-adjusted odds ratios were 1.5 (95% CI 1.2-1.9), 1.3 (1.0-1.7), and 1.3 (1.0-1.6) per SD increase of systolic blood pressure, BMI, and total cholesterol concentration, respectively, and 1.2 (1.0-1.5) per 50% increase of triglyceride level. Elevated blood pressure and plasma total and LDL cholesterol levels showed associations with retinal hard exudates.Conclusions: Retinopathy is a multifactorial microvascular complication, which, apart from hyperglycemia, is associated with blood pressure, lipid concentrations, and BMI. [ABSTRACT FROM AUTHOR]

Objective: While the apolipoprotein E ε 4 allele (ApoE- ε 4) is related to cognitive and brain decline in the general population, its effect on the brain in type 1 diabetes mellitus (T1DM) remains unclear. Therefore, the aim was to determine the interaction between ApoE- ε 4 and T1DM on cognitive performance and hippocampal structure and connectivity as the brain area most vulnerable to ApoE- ε 4 effects in adult patients with T1DM., Research Design and Methods: Blood sampling was performed in 104 patients with T1DM and 49 control subjects for ApoE genotyping, neuropsychology, and neuroimaging to determine hippocampal volume and resting-state connectivity. The interaction between T1DM status and ApoE- ε 4 presence was investigated and adjusted for age and mean systolic blood pressure., Results: ApoE genotyping could not be performed for three patients with T1DM. Significant interaction effects, indicating a differential effect of ApoE-ε4 between both groups, were found for overall cognitive functioning and for the subdomains of information processing speed and attention. Additionally, interaction effects were present for right hippocampal connectivity with the right posterior cingulate and supramarginal gyri. Subsequent group analysis showed that patients with T1DM with ApoE- ε 4 performed worse on these cognitive domains with increased connectivity, relative to their counterparts without ApoE- ε 4. In contrast, no cognitive effects, but decreased connectivity, were observed in control subjects with ApoE- ε 4. In patients with T1DM, higher right hippocampus connectivity with the posterior cingulate gyrus was related to poorer overall cognitive functioning., Conclusions: The results may suggest that ApoE-ε4 presence leaves our patients with T1DM more susceptible to cognitive decrements at a younger age, possibly through vascular pathways, warranting further longitudinal studies., (© 2021 by the American Diabetes Association.)

Objective: Depression is common in patients with type 2 diabetes and adversely affects quality of life and diabetes outcomes. We assessed whether light therapy, an antidepressant, improves mood and insulin sensitivity in patients with depression and type 2 diabetes., Research Design and Methods: This randomized, double-blind, placebo-controlled trial included 83 patients with depression and type 2 diabetes. The intervention comprised 4 weeks of light therapy (10,000 lux) or placebo light therapy daily at home. Primary outcomes included depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and insulin sensitivity (M-value derived from the results of a hyperinsulinemic-euglycemic clamp). Secondary outcomes were related psychological and glucometabolic measures., Results: Intention-to-treat analysis showed that light therapy was not superior to placebo in reducing depressive symptoms (-3.9 IDS points [95% CI -9.0 to 1.2]; P = 0.248) and had no effect on insulin sensitivity (0.15 mg/kg*min [95% CI -0.41 to 0.70]; P = 0.608). Analyses incorporating only those participants who accurately adhered to the light therapy protocol ( n = 51) provided similar results, but did suggest positive effects of light therapy on depression response rates (≥50% reduction in IDS points) (26% more response; P = 0.031). Prespecified analysis showed effect moderation by baseline insulin sensitivity ( P = 0.009) and use of glucose-lowering medication ( P = 0.023). Light therapy did not affect depressive symptoms in participants with higher insulin sensitivity or those who use only oral glucose-lowering medication or none at all, but it did produce a relevant effect in participants with lower insulin sensitivity (-12.9 IDS points [95% CI -21.6 to -4.2]; P = 0.017) and a trend toward effectiveness in those using insulin (-12.2 IDS points [95% CI -21.3 to -3.1]; P = 0.094). Light therapy was well tolerated., Conclusions: Although this trial is essentially inconclusive, secondary analyses indicate that light therapy might be a promising treatment for depression among a subgroup of highly insulin-resistant individuals with type 2 diabetes., (© 2019 by the American Diabetes Association.)

Objective: Patients with longstanding type 1 diabetes may develop microangiopathy due to high cumulative glucose exposure. Also, chronic hyperglycemia is related to cerebral alterations and cognitive dysfunction. Whether the presence of microangiopathy is conditional to the development of hyperglycemia-related cerebral compromise is unclear. Since subcortical, rather than cortical, volume loss was previously related to cognitive dysfunction in other populations, we measured these brain correlates and cognitive functions in patients with longstanding type 1 diabetes with and without microangiopathy., Research Design and Methods: We evaluated differences in subcortical volume and cortical thickness and volume in type 1 diabetic patients with (n = 51) and without (n = 53) proliferative retinopathy and 49 control subjects and related volume differences to cognitive dysfunction. Analyses were corrected for age, sex, systolic blood pressure, and A1C., Results: Putamen and right thalamic volume loss was noted in both patients with and without proliferative retinopathy compared with control subjects (all P < 0.05). Additionally, in patients with proliferative retinopathy relative to control subjects, volume loss of the bilateral nucleus accumbens was found (all P < 0.05). No differences were observed between the two patient groups. Cortical thickness and volume were not different between groups. In pooled analyses, lower left nucleus accumbens volume was associated with cognitive dysfunction (P < 0.035)., Conclusions: This study shows subcortical, but not cortical, volume loss in relation to cognitive dysfunction in patients with longstanding type 1 diabetes, irrespective of microangiopathy. The time course, pathophysiology, and clinical relevance of these findings need to be established in longitudinal and mechanistic studies., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

OBJECTIVE We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS Thirty-three patients with proliferative diabetic retinopathy (PDR+), 34 patients without proliferative diabetic retinopathy, and 33 controls underwent magnetic resonance imaging to assess cerebral microangiopathy (cerebral microbleeds) and ischemic damage (white matter hyperintensities and lacunes). Peripheral microvascular function, i.e., skin capillary density and capillary recruitment, was assessed by capillary microscopy. RESULTS Cerebral microbleeds, but not ischemic damage, were more prevalent in PDR+ patients versus the other groups (P < 0.05). A trend was found across groups for the lowest baseline capillary density in PDR+ patients (P for trend = 0.05). In individuals with microbleeds, capillary recruitment was impaired compared with those without microbleeds (P = 0.04). CONCLUSIONS In PDR+ patients, cerebral microbleed prevalence was higher and seems part of generalized microangiopathy that may affect the skin and the brain.

Objective: To identify distinct developmental patterns of diabetic retinopathy (DR) and assess the risk factor levels of patients in these clusters., Research Design and Methods: A cohort of 3,343 patients with type 2 diabetes mellitus (T2DM) monitored and treated in the Diabetes Care System West-Friesland, the Netherlands, was followed from 2 to 6 years. Risk factors were measured, and two-field fundus photographs were taken annually and graded according to the EURODIAB study group. Latent class growth modeling was used to identify distinct developmental patterns of DR over time., Results: Five clusters of patients with distinct developmental patterns of DR were identified: A, patients without any signs of DR (88.9%); B, patients with a slow regression from minimal background to no DR (4.9%); C, patients with a slow progression from minimal background to moderate nonproliferative DR (4.0%); D, patients with a fast progression from minimal or moderate nonproliferative to (pre)proliferative or treated DR (1.4%); and E, patients with persistent proliferative DR (0.8%). Patients in clusters A and B were characterized by lower risk factor levels, such as diabetes duration, HbA(1c), and systolic blood pressure compared with patients in progressive clusters (C-E)., Conclusions: Clusters of patients with T2DM with markedly different patterns of DR development were identified, including a cluster with regression of DR. These clusters enable a more detailed examination of the influence of various risk factors on DR.