Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Fructosamine as a predictor of incident diabetic microvascular disease in a population with high prevalence of red cell disorders: A cohort study.

AIMS: Fructosamine can be used to estimate glycaemia in individuals in whom HbA1c may be unreliable. We aimed to establish clinically useful fructosamine treatment targets in a population with a high prevalence of conditions affecting erythrocyte survival, including variant haemoglobin and G6PD deficiency. METHODS: Fructosamine was measured on a clinical basis in individuals in whom HbA1c was suspected to be unreliable by their primary physician. Study endpoints were incident retinopathy and albuminuria in individuals with Prediabetes (n = 60), Type 1 (n = 161) or Type 2 diabetes (n = 1350) during follow up of 4.4 ± 2.3 years. RESULTS: Fructosamine ≥ 250 umol/L was significantly associated with incident retinopathy, and fructosamine ≥ 300 umol/L with incident microalbuminuria, in univariate analysis and adjusted for established risk factors. Fructosamine ≥ 250 umol/L was also significantly associated with incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol) at inclusion. CONCLUSIONS: In this patient population, a single measurement of fructosamine significantly and independently predicts incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol). Routine measurement of fructosamine on at least one occasion is recommended as part of assessment of prediabetes or diabetes mellitus in populations with a high prevalence of conditions affecting erythrocyte lifespan.

Parameters of Bone and Cardiovascular Health Related to 25-Hydroxyvitamin D Status in Emirati Nationals attending Primary Care and Diabetes services: a retrospective cohort study.

Vitamin D deficiency is endemic in people living in the Gulf states. We performed a retrospective analysis of data gathered at the first attendance of 82,396 Emirati nationals to outpatient diabetes, endocrinology and general primary care services at two centres in the United Arab Emirates during 2012-2016. Our aim was to explore associations between vitamin D status and markers of cardiovascular and bone health. In the study population, 67.1% of men and 73.5% of women had serum 25(OH)D of less than 50 nmol/L, with the lowest levels being found in young adults. Among Emirati adults with type 2 diabetes, serum 25(OH)D < 50 nmol/L was associated with an increased risk of a coexisting adverse total cholesterol:HDL (TC:HDL) ratio (odds ratio 2.13 (1.60-2.84), p < 0.001). Correcting for age, sex, body mass index, HbA1c and statin therapy, an increase in 25(OH)D of 1 nmol/L was associated with a 0.01 unit reduction in TC:HDL in this population. In a subset of 1064 adult individuals, 25(OH)D < 25 nmol/L was associated with a reduction in DEXA-measured z-score of -0.29 (-0.44 to -0.15, p < 0.001) at the femoral neck and of -0.25(-0.45 to -0.05, p = 0.015) at L1-4, corrected for body mass index, compared with individuals with 25(OH)D ≥ 75 nmol/L. Our findings raise concerns regarding lifetime burden of cardiovascular disease and bone health for young Emiratis with vitamin D deficiency.

Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints.

Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.

The effects of Ramadan fasting on activity and energy expenditure.

Background: Fasting during the month of Ramadan entails abstinence from eating and drinking between dawn and sunset and a major shift in meal times and patterns with associated changes in several hormones and circadian rhythms; whether there are accompanying changes in energy metabolism is unclear. Objective: We have investigated the impact of Ramadan fasting on resting metabolic rate (RMR), activity, and total energy expenditure (TEE). Design: Healthy nonobese volunteers (n = 29; 16 women) fasting during Ramadan were recruited. RMR was measured with the use of indirect calorimetry. In subgroups of participants, activity (n = 11; 5 women) and TEE (n = 10; 5 women) in free-living conditions were measured with the use of accelerometers and the doubly labeled water technique, respectively. Body composition was measured with the use of bioelectrical impedance. Measurements were repeated after a wash-out period of between 1 and 2 mo after Ramadan. Nonparametric tests were used for comparative statistics. Results: Ramadan fasting did not result in any change in RMR (mean ± SD: 1365.7 ± 230.2 compared with 1362.9 ± 273.6 kcal/d for Ramadan and post-Ramadan respectively, P = 0.713, n = 29). However, controlling for the effects of age, sex, and body weight, RMR was higher in the first week of Ramadan than in subsequent weeks. During Ramadan, the total number of steps walked were significantly lower (n = 11, P = 0.001), while overall sleeping time was reduced and different sleeping patterns were seen. TEE did not differ significantly between Ramadan and post-Ramadan (mean ± SD: 2224.1 ± 433.7 compared with 2121.0 ± 718.5 kcal/d for Ramadan and post-Ramadan, P = 0.7695, n = 10). Conclusions: Ramadan fasting is associated with reduced activity and sleeping time, but no significant change in RMR or TEE. Reported weight changes with Ramadan in other studies are more likely to be due to differences in food intake. This trial is registered at clinicaltrials.gov as NCT02696421.

Environmental determinants of previtamin D synthesis in the United Arab Emirates.

Despite abundant sunshine throughout the year, vitamin D deficiency is endemic in the UAE. Solar radiation within the UVB range of the spectrum is required for the photosynthesis of previtamin D3 in the skin. Atmospheric transmission of UVB is strongly influenced by atmospheric conditions and solar zenith angle. We investigated the effects of diurnal and seasonal variation on the availability of sufficient UVB radiation for adequate previtamin D3 synthesis using an established in vitro model. Borosilicate ampoules of 7-dehydrocholesterol, the precursor of previtamin D3, in ethanol (50 µg/mL) were exposed to direct sunlight in an urban area of Abu Dhabi, at one hourly intervals between 0800 and 1700, on one day of each month over a period of one year. Conversion to previtamin D3, vitamin D3 and metabolically inactive photoisomers was analyzed using high performance liquid chromatography. The efficiency of 7-dehydrocholesterol conversion to previtamin D3 varied estimated UVB intensity. At the latitude of Abu Dhabi (24.2 N) previtamin D3 synthesis can occur throughout the year. However very little if any previtamin D3 was produced before 0900 hrs.and after 1600 hrs. Local conditions in Abu Dhabi are likely sufficient to maintain vitamin D levels throughout the year given adequate sun exposure.