Novel sexual dimorphisms of sleep apnea syndrome in diabetes.

BACKGROUND: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM. METHODS: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into OSAS[-] and OSAS[+] were assessed for cardiometabolic risk factors, glucose homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD); and GAD65 antibodies. RESULTS: There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate. CONCLUSION: We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM.

What are the characteristics of phenotypic type 2 diabetic patients with low-titer GAD65 antibodies?

Type 2 diabetes results from combined insulin resistance and ß-cell deficiency. Type 1 diabetes results from ß-cell destruction associated with islet autoantibodies, including those directed against glutamate decarboxylase (GAD65 antibodies [GADA]). Clinical impact of low GADA positivity (<60 U/ml) in type 2 diabetes is debated, being rarely performed in routine care. The aim of our study was to determine the prevalence and cardiometabolic/autoimmune phenotype of GADA[+] patients. 524 type 2 diabetes consecutive outpatients were assessed for glucose homeostasis using homeostasis model assessment (HOMA): insulin sensitivity (HOMA S); ß-cell function (HOMA B) and annualized loss in [BXS]. GADA prevalence was 6% (n = 30). There were no differences between groups for age, diabetes duration and family history of diabetes. There were proportionately more women (33 vs. 53%) in GADA[+]. There were no differences in body mass index, waist circumference or visceral fat. HOMA S was lower than normal, with no difference between groups, as was HOMA B. Annualized rate of [BXS] loss was 1.26%/year (GADA[+]) versus 1.34%/year (GADA[-]; NS). HbA1c was 7.8% (GADA[+]) versus 7.6% (GADA[-]; NS). Among all patients, prevalence of autoimmune thyroid disease was 10%. In GADA[+], this prevalence was significantly increased and equally affected both sexes: 29% (men) versus 25% (women), while for GADA[-] the prevalence was 5% (men) versus 18% (women; p < 0.0001). Low-titer GADA autoimmunity among type 2 diabetes patients was not associated with accelerated ß-cell function, nor with any distinctive cardiometabolic phenotype, but for a markedly increased prevalence of autoimmune thyroid disease, especially among men.

Sleep apnoea syndrome and 10-year cardiovascular risk in females with type 2 diabetes: relationship with insulin secretion and insulin resistance.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is a risk factor for type 2 diabetes mellitus (T2DM) and promotes cardiovascular events, especially in men. The prevalence of sleep apnoea and its association with microvascular and macrovascular diseases and glycaemic control are poorly documented in T2DM women. METHODS: A total of 305 T2DM women were sleep apnoea diagnosed through (hetero)anamnesis, Epworth's score, oximetry and polysomnography. Sleep apnoea[+] (n = 25) were compared with sleep apnoea[-] (n = 280) regarding cardiovascular risk factors, glucose homeostasis, micro/macrovascular complications and the United Kingdom Prospective Diabetes Study (UKPDS) 10-year risk. RESULTS: Mean (1 SD) age was 66 (12) years, diabetes duration 15 (9) years, sleep apnoea prevalence 8.2% and metabolic syndrome 86%. There were no differences in age, diabetes duration, education, smoking and blood pressure between groups. Sleep apnoea[+] had significantly higher values of body mass index, waist, relative/absolute fat, conicity, visceral fat (all p < 0.0001) and lower skeletal muscle (p = 0.0008). The sleep apnoea[+] group was more insulin resistant [homeostasis model assessment (HOMA S): 37 (20)% versus 59 (44)%; p < 0.0001] and had lesser residual insulin secretion (HOMA B × S: 20 (12)% versus 30 (19)%; p = 0.0006), increased hyperbolic product loss (p = 0.0442) and poorer glycaemic control (HbA1c 69 (12) versus 62 (13) mmol mol(-1) ; p = 0.0099). All atherogenic dyslipidaemia components and inflammatory markers were worsened in sleep apnoea[+]. Women with sleep apnoea had higher UKPDS risk of CAD: 18 (11)% versus 12 (10)% (p = 0.0136). Prevalent micro/macrovascular complications were not different between groups. CONCLUSIONS: Sleep apnoea, a frequent comorbidity of T2DM women, is associated with central fat, atherogenic dyslipidaemia, inflammation, worsening ß-cell function, poorer glycaemic control and coronary artery disease risk. Sleep apnoea may increase residual vascular risk for microvascular and macrovascular events in T2DM women.