الفهرس 
ObesityOnly 14 pages are availabe for public view
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Abstract
In conclusion, in vitamin D deficient pre- diabetic obese, 25 (OH) D levels negatively correlated with HOMA-IR and LDL-C and triglycerides after vitamin D supplementation. These results may help highlight the importance of vitamin D supplementation to improve insulin secretion and insulin sensitivity, thereby indirectly influencing lipid metabolism and eventually prevention of atherosclerosis and cardiovascular mortality.
Recommendations
Similar studies should be conducted with a larger sample size and with different age groups.
Longterm effects should be tested by a frequent and longitudinal series of measurements to evaluate the results.
Further studies are needed to confirm the effects of vitamin D supplementation on insulin resistance and dyslipidemia in obese individuals.
Summary
Obesity is a chronic, progressive, relapsing, and treatable multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.it is considered to be the second most common, and may soon become, the most common preventable cause of cancer, overtaking cigarette smoking.
Its incidence has tripled in the last few decades, such that more than two thirds (70.2%) of the United States adult population is overweight or obese and almost half of adults (48.5%) live with prediabetes or diabetes. Obesity dramatically increases the risk for type 2 diabetes and both conditions represent major public health issues worldwide according to the latest reports from World Health Organization (WHO report 2020 and 2021).
Continuous excessive energy intake leads to hypertrophy of adipocytes due to excessive triglyceride storage in the liver and muscle tissues, impairment of insulin secretion occurs due to the interaction with the insulin signaling cascade and increased apoptosis of pancreatic beta cells, and insulin resistance is induced.
Insulin resistance arises when the nutrient storage pathways evolved to maximize efficient energy utilization are exposed to chronic energy surplus. Ectopic lipid accumulation in liver and skeletal muscle triggers pathways that impair insulin signaling, leading to reduced muscle glucose uptake and decreased hepatic glycogen synthesis. Muscle insulin resistance, due to ectopic lipid, precedes liver insulin resistance and diverts ingested glucose to the liver, resulting in increased hepatic de novo lipogenesis and hyperlipidemia. Subsequent macrophage infiltration into white adipose tissue (WAT) leads to increased lipolysis, which further increases hepatic triglyceride synthesis and hyperlipidemia due to increased fatty acid esterification
Pre-diabetes is frequently associated with obesity and other components of metabolic syndrome.The prevalence of pre-diabetes is more than type 2 diabetes in all ages, sexes, and race/ethnic groups, in almost all parts of the world. Pre-diabetes is a stage where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes.
Pre-diabetes is defined as impaired fasting glucose (IFG) and/ or impaired glucose tolerance (IGT). Pre-diabetes is an intermediate stage between normal glucose tolerance and type 2 diabetes mellitus.
Obesity in turn is commonly associated with hypovitaminosis-D due to the capacity of adipose tissue to store 25(OH) D, making it biologically unavailable(Palomer et al., 2008) A decreased amount of serum 25(OH)D, calcitriol [1,25(OH)2D] and raised parathyroid hormone (PTH) can increase intracellular calcium in adipocytes, which can stimulate lipogenesis predisposing a patient to further weight gain and thus increasing the risk of diabetes.
Researchers have discovered that vitamin D receptors are located all over your body, including the pancreas, which produces insulin and plays a key role in the onset of diabetes.
Many Cross sectional and case control studies suggest an inverse association between vitamin D status, glucose intolerance and type 2 diabetes(Scragg et al., 2004).This could be due the distribution of Vitamin D receptors (VDR) on pancreatic beta cells, adipose tissue and skeletal muscle. Vitamin D status influences insulin secretion or insulin sensitivity. The effect of vitamin D on insulin secretion may be mediated by changes in intracellular calcium concentration in beta cells (Danescu et al., 2009). Vitamin D improves insulin sensitivity by its anti-inflammatory activity. Vitamin D attenuates the expression of proinflammatory cytokines involved in insulin resistance (IR) such as interleukins 1 and 6, TNF-alpha, also down regulates NF-Kappa b activity(Giulietti et al., 2007).Vitamin D deficiency impairs insulin sensitivity by increasing parathyroid hormone (PTH) levels(Teegarden and
The present study aims to investigate the relationship between vitamin D state and insulin resistance and whether a vitamin D supplementation combined with a hypo -caloric diet could have an effect on insulin resistance in subjects with both obesity and hypovitaminosis D.
Objectives: The study was conducted to determine the effect of vitamin D supplementation on obesity induced insulin resistance in pre -diabetic obese patients.
Subjects and methods: A randomized controlled study was carried out on forty- two vitamin D deficient pre-diabetic insulin resistant obese patients presented in obesity unit of Physical medicine, Rheumatology and Rehabilitation department in Ain Shams University Hospitals in the period from the end 2019 to until the end of July 2021. Data collection was done in randomly chosen days every week.The sample size was calculated using
Inclusion criteria:
• Age ranged from 30-50 years.
• Sex: Males and Females (single/ married, with /without children)
• Body mass index (BMI) ranged from 30-40 kg/m2.
• Pre- diabetics with insulin resistance.
Diagnosed by:
- Fasting blood sugar: 100-125mg/dl
- HbA1C: 5.7-6.4 %.
- Homeostatic model assessment- insulin resistance (HOMA-IR) > 3.i.e moderate to severe insulin resistance according to Mathews et al., 1985.
• Vitamin D deficient with Vitamin D level <20 ng/ml (according to endocrine society guidelines 2011).
Exclusion criteria:
• Diabetes Mellitus
• Any medical condition that may lead to secondary obesity as Polycystic ovary syndrome, Hypothyrodism and Cushing syndrome
• Any medical condition that could possibly affect vitamin D level: as Parathyroid disease, Hepatic or renal disease, Malabsorption syndrome, Sun light allergies, Pregnancy and Cancer
• History of medications that may alter weight or vitamin D level:
Medications documented to increase weight gain: as phenothiazines and butyrophenones, Antiepileptics and antidepressant (tricyclic antidepressant, valproate, carbamazepine), Steroids and Oral contraceptive pills.
Medications that affect vitamin D levels as Orlistat, Statins, Steroids, Thiazide diuretics, Anti- epileptics, Anti-diabetics, Rifampicin and Calcium supplementation.
The study was approved by Ain Shams medical ethical committee. Patients who met the eligibility criteria and agreed to participate in the study received a general explanation of the trial and signed an informed consent
Data were collected through:
Full medical history, which included Socio-demographic data (age, gender, education, etc.), Special habits of medical importance e.g. smoking, medical history, family history, previous surgical operations and regular medications.
Nutritional history: 24 hours dietary Recall or Food Diary:Including type of food, amount of food, numbers of meals and their timing and the time of last meal taken.
Sun light exposure and Physical activity details A detailed sunlight exposure questions to record nature of the work, direct sunlight exposure in minutes per day, clothing pattern, and categorized into the exposure of 10 minutes to one hour or more than one hour, together with recording indoor and outdoor activity
Full clinical examination including general physical examination for hirsutism in women, abdominal obesity, nail ridges, dry skin, dark skin on the back of the neck, underarms or between the thighs, thyroid tenderness or goiter (hypothyroidism) andskin findings of endocrinal disease, including: striea, acne and Hirsutism, dry or coarse skin and hair.
- Cardiac, Abdominal, locomotor and chest examination were done.
Anthropometric Measurements: Weight was measured by a digital scale. Standing height was measured in a stretch stature using a stadiometer or a measuring tape. Body mass index (weight/height “m2”) was calculated (WHO, 2006).together with body composition assessment including body fat and muscle mass by bioelectric impedance device.
Comprehensive metabolic assessment that included serum calcium and phosphorus, lipid profile, fasting blood sugar, Hb A1c and liver and kidney function tests.
Hormonal assessment of vitamin D, T4, parathyroid hormone and insulin and HOMA-IR is calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA- IR):
Fasting Insulin (μIU/mL) × Fasting Blood Glucose (mg/dL) /405
After completing the assessment, the vitamin D deficient insulin resistant obese patients were randomly divided into two groups, twenty one each, group 1 received a hypo-caloric (500-kcal deficit diet) (vitamin D rich) diet personalized according to the total energy expenditure (TEE) together with vitamin D Supplementation of oral vitamin D3 for 12 weeks in the form of A loading dose: 50, 000 IU per week for 2 months followed by a maintenance dose: 25, 000 IU per week for 1 month to achieve a higher blood level of 25 (OH) D. To guarantee medication adherence, we while group 2 received a hypo-caloric (500-kcal deficit diet) (vitamin D rich) diet personalized according to TEE.
Adherence was assessed by records of total energy intake and expenditure by the participants and by regular weekly check of weight loss and supervise vitamin D administration during attendance at the weight management clinic, and patients were revaluated for any change in weight, insulin resistance and vitamin D level together with any change in detailed body composition after 12 weeks.
Results:
Vitamin d supplementation together with a weight loss program resulted in a significant increase of serum vitamin D, and significant decrease in weight, triglyceride level, fasting blood sugar and HOMA-IR level compared to the baseline levels in the vitamin d supplementation group (group 1).Weight, BMI and HOMA-IR decreased in both groups.
Between the two groups there was a statistically significant difference in relative change (baseline to post intervention levels) of weight, BMI, HOMAI-IR, fasting blood sugar and triglyceride level and a statistically non-significant difference in relative change of fat and muscle mass.
A statistically significant negative correlation was found between vitamin D change and HOMA-IR change, triglycerides level change and fasting insulin change of P value 0.032, 0.020 and 0.002 and with r value -0.332, -0, 359 and -0.463 respectively and between vitamin d change and weight and BMI change of P value 0.008 and <0.001* and with r value-0, 406 and -0.636 respectively.
Conclusion:
Weight loss and vitamin D supplementation for 12 weeks may act synergistically to reduce the insulin resistance and dyslipidemia in pre diabetic insulin resistant obese patients
Recommendations:
Conduct further studies with a larger sample size and on different age groups.
Long term effect study should with frequent longitudinal series of measurements would be of value in evaluating vitamin D value.
Further studies are needed to confirm the effects of vitamin D supplementation on insulin resistance and dyslipidemia in obese individuals.