CALCIUM AND DIABETES MELLITUS TYPE TWO A PROSPECTIVE STUDY DONE ON PEOPLE WITH TYPE 2 DIABETES IN DIWANIYA TEACHING HOSPITAL

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1 CALCIUM AND DIABETES MELLITUS TYPE TWO A PROSPECTIVE STUDY DONE ON PEOPLE WITH TYPE 2 DIABETES IN DIWANIYA TEACHING HOSPITAL DR. ALI MOHAMMED HUSSEIN AL-YASSIN CONSULTANT PHYSCIAN DIWANIYA TEACHING HOSPITAL Dr. ALI TALIB NIMNIM Medical College / AL QUADISYA University Medical Department Dr. EQBAL DOHAN CHALLAB AL-MA' AMON UNIVERCITY COLLEGE الخلاصة الخلف ة : الاخ تلال ف اي ض المع ادن ف ي م رض داء الس كري مع روف من ذ أكث ر م ن ثلاث ة عق أ ود. ون الكالس وم ل أ م ة في تنظ م نسبة السكري في الدم عن طر ق تا ث ره على صناعة وإفراز الا نسول ن من الخلا ا المع نة (خلا ا ب تا ( في البنكر اس. ال دف : لفحص نسبة أ ون الكالس وم في المرضى المصاب ن بداء السكري النوع الثاني في مد نة الد وان ة. الطر قة : س بعون م ر ض مص اب ب داء الس كري الن وع الث اني م ن مختل ف الا عم ار وك لا الجنس ن مع دل الا عمار SD±٥٦ ٢٣ وسبعون شخص أصحاء م ن كلا الجنس ن وبمع دل عمر ± ٣٦,٢ ١٤,٣ SD تم فحص نسبة السكر وأ ون الكالس وم قبل الفطور وبع ده الحص لة ي نسبة الكالس وم نسبة السكر الكولسترول والد ون الثلاث ة في الدم. النت جة : نس بة الكالس وم وج دت منخفض ة وبنس بة ملحوظ ة ف ي المرض ى المص اب ن ب داء الس كر مقارن ة با ش خاص أص حاء ذو نس بة س كر طب ع ة. انخف اض نس بة الكالس وم وج دت بمع دل % ٤٣ ف ي مرضى داء السكري. الاستنتاج : انخفاض نسبة الكالس وم وجد بنسبة ملحوظة في مرضى داء الس كر الغ ر مس طر عل ل ذا جب البحث عن نسبة الكالس وم في الدم وتصح ح ا لغرض تنظ م نسبة السكر في الدم. Abstractz Background: Disturbance in mineral metabolism in diabetes is well-known for the last three decades. Calcium ion plays an important role in glycemic control by affecting the biosynthesis and release of insulin from the Beta cells of the pancreas. Objective: To examine the level of serum calcium in patients with diabetes type 2 of different ages in Diwaniya city. Methods : seventy patients with diabetes type 2 of different ages and both sexes with a mean age of ±SD ± 8.25 years and seventy healthy controls of both sexes with a mean age of ± SD of years were examined for serum calcium and glucose 468

2 level in the fasting state and postprandial serum glucose level was done. Main outcome measures were serum calcium (scal), serum glucose (SGL), serum cholesterol, and serum triglyceride level in fasting state. Results : Serum calcium level was significantly lower in patients with type 2 diabetes as compared to normal healthy control persons with normal blood sugar. Hypocalcaemia was seen in 43% of our patients with type 2 diabetes. Conclusion : Hypocalcaemia is significantly associated with uncontrolled hyperglycemia in patients with type 2 diabetes and should be looked for and corrected to have a better control of the blood sugar. Key words: Type 2 diabetes mellitus, calcium, glucose, hypocalcaemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia. Introduction The incidence of diabetes type 2 is increasing at an alarming rate both nationally and worldwide with more than one million cases per year diagnosed in the US alone.although our current methods of treating diabetes has improved but prevention is preferable {1}. High intake of calcium and vitamin D, particularly from supplements may lower the risk of diabetes by 33% and over a billion people are vitamin D deficient.{2} A growing body of evidence on clinical and animal studies has linked insufficient level of vitamin D and calcium to a variety of human diseases such as osteoporosis,cancer and autoimmune diseases.{3,4} Based on basic and animal studies, vitamin D and calcium have been suspected as modifiers of diabetes risk. Vitamin D insufficiency has long been suspected as a risk factor for type 1 diabetes based on animal and human observational studies. More recently there is accumulating evidence to suggest that altered vitamin D and calcium homeostasis may also play a role in the development of type 2 diabetes {5}. An estimated 19 million people are affected by diabetes in Europe equal to four percent of the population and this figure is liable to increase to 28 million in 2030 {2}. In the United States there are 20 million people with diabetes, equal to seven percent of the population. The total costs are thought to be as much as 132$ billion with $92 billion results from direct cost of medications, according to 2002 American diabetic association figures {2}. The purpose of this study was to prospectively evaluate the association between calcium level in the blood and type 2 diabetes in comparison with normal healthy volunteers in a group of people of different age and in both sexes in Diwniya city. Patients and methods Seventy patients with type 2 diabetes of both sexes with a mean ±SD age of 56.23± 8.25 years who were attending the consultation department of Diwaniya Teaching hospital in Diwaniya city from August till September 2008 and seventy healthy nondiabetic control with a mean age ± SD of 36.2 ±14.3 years, were included in this study. No participant taking any minerals was included and diabetic patients with diarrhea, albuminuria and hypoalbiminemia were excluded from the study as serum calcium was correlated with normal serum albumin in our selected diabetic patients. The median range of the SGLand SCAL in control and type 2 diabetes is presented in table (1). The proportion of patients with hypocalcaemia in our study was 43% table (2). 469

3 Sugar Ca Control 89.93(mg/dl) 9.61(mg/dl) diabetic (mg/dl) 8.09(mg/dl) Table (1) Median range for the SGL and SCal in healthy controls and type 2 diabetes Venous blood samples were taken in the fasting state at 9 am. and post prandial glucose level was measured after 2 hours, blood collected in sterile unused glass test tubes and allowed to clot for 2 hours at room temperature. After centrifugation, the serum was removed. Glucose measured by spectrophotometric enzymatic end point method{6}. Serum calcium level was analyzed by dye colorimetric method, which uses O- cresolfalein complexone at alkaline ph. The intensity of the cromophore formed is proportional to the concentration of total calcium in the sample{7}. The kit purchased for the analysis of the data was from linear chemicals Barcelona (Spain). The accepted level of significance was at P < OCC +Calcium OCC calcium complex Results The normal referral values for serum calcium,serum glucose, serum cholesterol, serum triglyceride were as follows respectively, mg/dl, mg/dl, <200mg/dl, and mg/dl respectively. Serum calcium was low in 43% of the patient group studied with a (P<0.001) compared with the healthy controls (table 2and 3 ) while serum glucose, serum cholesterol, and serum triglycerides were all elevated as compared to the control (table 4and 5 ). Hypercholesterolemia was found in 50% of patients, while hypertriglyceridemia was found in 58.57% of the patients. hyperglycemia was found in 95.7%. There was a significant inverse correlation between the level of cholesterol, triglyceride and hypocalcaemia, patients with high serum cholesterol and triglyceride had lower serum calcium levels,with a reverse relationship and r value of for serum cholesterol and for the triglyceride level. 470

4 Table (2) shows the mean value for SCAL in both control and diabetic Table (3) shows the percentage of patients with hypocalcaemia 471

5 Table (4).the percentage of patients with hyperglycemia and hypocalcaemia compared to control Table (5) shows the mean levels of glucose,cholesterol,and triglyceride in Diabetic and control 472

6 Discussion There is evidence to suggest that altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes {8,9}. Both vitamin D and calcium intake are inversely associated with development of type 2 diabetes, and the effect of the two nutrients appears to be additive or synergistic. For both vitamins D intake and calcium from supplements rather than diet were associated with a lower risk of type 2 diabetes {8, 9, 10, 11}. Although the evidence to date suggests that vitamin D and calcium deficiency influences post prandial glycemia and insulin response while supplementation may be beneficial in regulating these processes,the exact mechanisms by which vitamin D and calcium may promote B cell function, or ameliorate insulin resistance is incomplete {8,9}. The mechanism by which vitamin D affect the risk of diabetes is not known. Both insulin resistance and impaired B cell function has been reported with vitamin D deficiency {13,23}. The mechanism by which calcium intake may alter diabetes risk are speculative.abnormal regulation of intracellular calcium affecting both insulin sensitivity and release has been suggested as a possible mechanism to explain the association between calcium insufficiency and the risk of diabetes{14,15}. The main mechanism of vitamin D is to enhance absorption of calcium from the intestine.therefore insufficient calcium results from insufficient vitamin D from low intake or from low calcium intake. this hypothesis is supported by data indicating that calcium is essential in normalizing glucose intolerance in vivo{16}.the additive effect of calcium and vitamin D intake suggests that increased vitamin D intake may potentiate the effect of calcium intake, but it does not rule out a direct effect of vitamin D independent of its role in calcium homeostasis Indeed,in vitro animal studies suggests that the effect of vitamin D on B- cell appears to direct and independent of plasma calcium concentration {17}. In this study we found the proportion of patients with type 2 diabetes who have hypocalcaemia was 43%, and the hypocalcemia correlated signifigantly with the height of both serum cholesterol anf triglyceride level, the higher the level of either of them the lower the calcium level was in the serum. Our finding was consistent with other studies which showed that hypocalcaemia was associated with both the development of metabolic syndrome and type 2 diabetes. In this study we found the proportion of patients with type 2 diabetes who have hypocalcaemia was 43%, and the hypocalcaemia correlated significantly with the height of both serum cholesterol and triglyceride level, the higher the level of either of them the lower the calcium level was in the serum. Our finding was consistent with other studies which showed that hypocalcaemia was associated with both the development of metabolic syndrome and type 2 diabetes [18,19,20,22] The limitation of our study is the small number of patients taken and the period for follow up, as we need a prolonged period following the consumption of adequate amount of both vitamin D and calcium to see the response of the patients and the control of their blood glucose. Currently recommended intakes for calcium are 1,200 mg/day for adults aged >50 years and for vitamin D are 400 IU/day for those aged years and 600 IU/day for those aged >70 years (21). However, there is growing consensus that vitamin D intakes above the current recommendations may be associated with better health outcomes. In relation to calcium intake for type 2 diabetes, the evidence suggests that intakes above 600 mg/day are desirable but intakes above 1200 mg may be optimal [22]. 473

7 Conclusion Serum calcium plays an important role in the regulation of glucose level in the blood particularly post- prandial glucose level, hence serum calcium should be measured in patients with type 2 diabetes who have uncontrolled hyperglycemia, and oral supplementation of both vitamin D and calcium from sources other than diet is recommended. References 1- Source: Journal of Clinical Endocrinology & Metabolism June 2007, Volume 92, Number 6, Pages doi: /jc "The Role of Vitamin D and Calcium in type 2 diabetes. A systematic Review and Meta-Analysis" Authors: A.G. Pittas, J. Lau, F. Hu, B. Dawson-Hughes 2- NUTRA USA Ingredients.com By STEPHEN DANIELLS 3-April Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84: Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81: Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab. 2005;16: Burtis, C.A., and Ashwood, E.R. ; Tietz Fundamentals of clinical chemistry.philadelephia; WB saunders, 1998: p,p, , Christenson, R.H. Gregory, L.C. and Johnson, L.J.; Appletone and Langens Outline Review Clinical Chemistry. New York: McGraw Hill Companies 2001 p.p Lind L, Pollare T, Hvarfner A, Lithell H, Sorensen OH, Ljunghall S: Long-term treatment with active vitamin D ( -calcidol) in middle-aged men with impaired glucose tolerance: effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. Diabetes Res 11: , Scragg R, Sowers M, Bell C: Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 27: , Orwoll E, Riddle M, Prince M: Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. Am J Clin Nutr 59: , Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R: The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 57: , Cade C, Norman AW: Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo. Endocrinology 119:84 90, Johnson JA, Grande JP, Roche PC, Kumar R: Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. Am J Physiol 267:E356 E360, Zemel MB: Nutritional and endocrine modulation of intracellular 3calcium: implications in obesity, insulin resistance and hypertension. Mol Cell Biochem 188: , Fujita T, Palmieri GM: Calcium paradox disease: calcium deficiency prompting secondary hyperparathyroidism and cellular calcium overload. J Bone Miner Metab 18: ,

8 16- Fujita T, Palmieri GM: Calcium paradox disease: calcium deficiency prompting secondary hyperparathyroidism and cellular calcium overload. J Bone Miner Metab 18: , Cade C, Norman AW: Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo. Endocrinology 119:84 90, Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006;29: McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med. 1992;93: Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338: Food and Nutrient Board IoM. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D and fluoride. Washington, DC: National Academy Press; Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care. 2005;28: Chiu KC, Chu A, Go VL, Saad MF: Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr79 : , Norman AW, Frankel JB, Heldt AM, Grodsky GM: Vitamin D deficiency inhibits pancreatic secretion of insulin. Science209 : , Isaia G, Giorgino R, Adami S: High prevalence of hypovitaminosis D in female type 2 diabetic population (Letter). Diabetes Care24 :1496, Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R: The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract57 : ,