C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial Supplementation of Vitamin C Reduces Blood Glucose and Improves Glycosylated Hemoglobin in Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis Higher heart rate may predispose to obesity and diabetes mellitus: 20-year prospective study in a general population. Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. Evaluation of aortic calcification with lanthanum carbonate vs. calcium-based phosphate binders in maintenance hemodialysis patients with type 2 diabetes mellitus: an open-label randomized controlled trial. Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy? Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. Effect of Activated Vitamin D on Glucoparameters in HCV Seropositive and Seronegative Patients on Chronic Hemodialysis Antioxidant Effects of Zinc Supplementation in Tunisians with Type 2 Diabetes Mellitus Vitamin D and calcium intake in relation to type 2 diabetes in women. Effect of oral supplementation of free amino acids in type 2 diabetic patients-- a pilot clinical trial. The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes Vitamin E Supplementation Reduces Cardiovascular Events in a Subgroup of Middle-Aged Individuals With Both Type 2 Diabetes Mellitus and the Haptoglobin 2-2 Genotype: A Prospective Double-Blinded Clinical Trial Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus. Serum IL-18 and hsCRP correlate with insulin resistance without effect of calcitriol treatment on type 2 diabetes. Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency
CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis Background Besides the classical role of vitamin D on calcium and bone homeostasis , vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus . However , it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus . There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control . The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus . Methods / design In a r and omised double-blind placebo-controlled trial conducted in five general practice s in the Netherl and s three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are r and omised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals . The primary outcome measure is the change in glycated haemoglobin level between baseline and six months . Secondary outcome measures include blood pressure , anthropometric parameters , lipid profile , insulin resistance , quality of life , advanced glycation end products and safety profiles . Quality of life will be measured by The Short Form ( SF-36 ) Health Survey question naire . Advanced glycation end products are measured by an AGE-reader . Discussion This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus . Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus . Trial registration The Netherl and s trial register : No study has ever examined the effect of vitamin C with metformin on fasting ( FBS ) and postmeal blood glucose ( PMBG ) as well as glycosylated hemoglobin ( HbA1c ) in the treatment of type 2 diabetes mellitus ( DM ) . The goal was to examine the effect of oral vitamin C with metformin on FBS , PMBG , HbA1c , and plasma ascorbic acid level ( PAA ) with type 2 DM . Seventy patients with type 2 DM participated in a prospect i ve , double-blind , placebo-controlled , 12-week study . The patients with type 2 DM were divided r and omly into placebo and vitamin C group of 35 each . Both groups received the treatment for twelve weeks . Decreased PAA levels were found in patients with type 2 diabetes mellitus . This level was reversed significantly after treatment with vitamin C along with metformin compared to placebo with metformin . FBS , PMBG , and HbA1c levels showed significant improvement after 12 weeks of treatment with vitamin C. In conclusion , oral supplementation of vitamin C with metformin  reverses ascorbic acid levels , reduces FBS , PMBG , and improves HbA1c . Hence , both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity . This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity . Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D ( 25(OH)D ) is inversely associated with insulin resistance , although direct measurements of insulin sensitivity are required for confirmation . Reported associations with insulin secretion , however , are contradictory . Available prospect i ve studies support a protective influence of high 25(OH)D concentrations on type 2 diabetes mellitus risk . There is a general lack of consistency in vitamin D intervention outcomes on insulin secretion and sensitivity , likely due to differences in subject population s , length of interventions , and forms of vitamin D supplementation . Vitamin D receptor gene polymorphisms and vitamin D interactions with the insulin like growth factor system may further influence glucose homeostasis . The ambiguity of optimal vitamin D dosing regimens and optimal therapeutic concentrations of serum 25(OH)D limit available intervention studies . Future studies , including cross-sectional and prospect i ve , should be performed in population s at high risk for both vitamin D deficiency and type 2 diabetes mellitus . Well- design ed , placebo-controlled , r and omized intervention studies are required to establish a true protective influence of  vitamin D on glucose homeostasis BACKGROUND Emerging evidence indicates an association between sympathetic activation and metabolic syndrome . However , sympathetic activation in metabolic syndrome may be a cause , consequence , or just epiphenomenon . To eluci date this issue , the predictive power of resting heart rate for the development of abnormal glucose and lipid metabolisms after 20 years was evaluated in a general population . METHODS A total of 637 participants ( > 20 years old ) underwent a health examination in 1979 including measurements of blood chemistries . Resting heart rate ( bpm ) was measured by an electrocardiogram .  In 1999 , all of the study participants again underwent a health examination , including electrocardiogram and blood chemistries .  Because four of them had atrial fibrillation , and 19 subjects were taking antihypertensive medication in 1979 , they were excluded from analysis . Therefore , a complete data set of 614 subjects was available . RESULTS As was reported in our previous article , in 1999 we found a linear and significant ( P < 0.05 ) cross-sectional relationship between resting heart rate and a cluster of cardiometabolic risk factors ( blood pressure ( BP ) , free fatty acid ( FFA ) , plasma glucose , and homeostasis model assessment ( HOMA ) index ) . Baseline higher heart rate ( heart rate > or=80 bpm in 1979 ) predicted the development of obesity , diabetes mellitus ( DM ) , and insulin resistance in 1999 after adjustments for age , sex , and other confounders . CONCLUSION This is one of the first prospect i ve reports demonstrating that higher heart rate may predispose to the development of obesity and DM , suggesting that the sympathetic nerve system may play a role in the development of obesity and DM Background : Diabetes mellitus ( DM ) and vitamin D deficiency are major health concerns around the world . Evidence suggests a possible role of vitamin D in improvement of insulin secretion and sensitivity . Objectives : We assessed whether vitamin D supplementation could be used in vitamin D deficient-type II diabetes to improve glucose metabolism , components of metabolic syndrome ( MetS ) and specific inflammatory biomarkers . Patients and Methods : A double blind , r and omized clinical trial was conducted in King Khalid University Hospital , Saudi Arabia to evaluate the effect of cholecalciferol supplementation on glycemic control , MetS components and specific inflammatory biomarkers including tumor necrosis factor-alpha ( TNF-α ) , Interleukin ( IL-6 ) , leptin , adiponectin and vascular cell adhesion molecule-1 ( VCAM-1 ) . Twenty-two patients with type II diabetes with insulin resistance , glycated hemoglobin ( HbA1c ) ≥ 6 ( 42 mmol/mol ) and serum 25(OH)D < 50 nmol/L were r and omized using a computer program to receive either supplementation with cholecalciferol ( 5000 IU/day ) or placebo for 12 weeks . The primary outcome was change in HbA1c levels from baseline . Results : Median [ IQR ] 25(OH)D levels increased significantly in the vitamin D group as 58.1 [ 48 , 67.3 ] nmol/L ( P = 0.002 ) . There was no significant difference in the change of HbA1c between the groups ( P = 0.5 ) with a decrease of -0.1 % [ -1 , 0.5 ] in the vitamin D group and an increase of 0.15 % [ 0.1 , 0.2 ] in the placebo group . A significant improvement was observed in the homeostasis model of assessment of β-cell activity ( HOMA-%B ) ( P = 0.03 ) with vitamin D supplementation compared to baseline . Conclusions : Vitamin D repletion for 12 weeks increased serum vitamin D concentrations and improved β-cell activity in vitamin D-deficient type II diabetes with no significant changes in HbA1c or insulin sensitivity AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) .  Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P<0.01 ) and systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P<0.01 ) but not diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P<0.01 ) in subjects with diabetes . Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol Vascular calcification ( VC ) contributes to cardiovascular disease in hemodialysis ( HD ) patients , especially with diabetes mellitus ( DM ) complications . No r and omized studies have been published regarding the effect of lanthanum carbonate ( LC ) on VC progression in DM patients . The aim of this study was to evaluate the effects of lanthanum carbonate on the progression of VC in HD patients with type 2 DM . We conducted a r and omized controlled trial comparing LC with calcium carbonate ( CC ) in 43 HD patients at a single dialysis center . Estimations of aortic calcification index ( ACI ) by abdominal computed tomography were performed twice for each patient ( at baseline and 12 months ) . Forty-one patients completed the study ( 19 LC , 22 CC ) . When ACI at baseline was ≦0.48 ( median of baseline ACI ) , median change in ACI ( Δ%ACI ) was 20.44 ( 11.50 - 36.80 % ) in the LC group , and 40.00 ( 33.30 - 92.60 % ) in the CC group ( P = 0.026 ) . On the other h and , when ACI at baseline was > 0.48 , the median change in ACI ( Δ%ACI ) was 6.42 ( 3.13 - 24.40 % ) in the LC group , and 8.08 ( 5.68 - 12.20 % ) in the CC group ( P = 1.000 ) . Serum markers of chronic kidney disease-mineral and bone disorder ( CKD-MBD ) , HbA1c , dose of vitamin D analogues , and side-effects of medications did not change in either group throughout the study except int-PTH increased in the LC group . This study indicated that administration of LC inhibited the progression of VC in patients receiving HD for type 2 DM , only in cases of slight VC compared with CC BACKGROUND Diastolic dysfunction is considered the first marker of diabetic cardiomyopathy . However , pre clinical systolic alteration was also recently described by strain , but its association with diastolic dysfunction has never been investigated . METHODS One hundred fourteen patients with type 2 diabetes mellitus ( DM ) with controlled blood pressure and without overt heart disease were prospect ively enrolled and compared with 88 age-matched controls . All subjects underwent comprehensive echocardiography , including diastolic evaluation according to current recommendations and speckle-tracking imaging . The prevalence of diastolic dysfunction , the determinants of diastolic parameters , and the association between pre clinical systolic and diastolic dysfunctions were studied . RESULTS Diastolic parameters were altered in patients compared with controls , with lower E/A ratios , longer mitral deceleration and isovolumic relaxation times , and higher E/e ' ratio . Diastolic dysfunction occurred in 47 % of patients with DM ( 33 % and 14 % with grade I and II diastolic dysfunction , respectively ) and systolic alteration ( longitudinal strain ≥ -18 % ) in 32 % of patients . Whereas longitudinal systolic strain was independently associated with DM and gender , diastolic parameters were influenced by many factors , including age , rate-pressure product , history of hypertension , and body mass index . Systolic alteration occurred in 28 % of patients with DM with normal diastolic function and in 35 % with diastolic dysfunction . CONCLUSIONS Diastolic dysfunction diagnosed according to current recommendations is frequent in patients with DM but is also influenced by other factors . Systolic strain alteration may exist despite normal diastolic function , indicating that diastolic dysfunction should not be considered the first marker of a pre clinical form of diabetic cardiomyopathy BACKGROUND Gastrointestinal ( GI ) tract symptoms are common among patients with diabetes mellitus ( DM ) seen in tertiary care centers . The degree to which this reflects referral bias is unclear . OBJECTIVES To determine whether GI tract symptoms are more prevalent in unselected patients with DM from the general community compared with their age- and sex-matched counterparts without DM and to assess the association of GI tract symptoms in persons with DM with psychosomatic symptoms , medication use , and symptoms of autonomic neuropathy . METHODS In this population -based , cross-sectional study , Olmsted County , Minnesota , residents with type 1 DM , a r and om sample of residents with type 2 DM , and 2 age- and sex-stratified r and om sample s of nondiabetic residents ( total of 1262 person for the 4 groups ) were mailed a previously vali date d symptom question naire . RESULTS Heartburn was less common in residents with type 1 DM vs controls ( 12 % vs 23 % ; P<.05 ) . No significant difference in prevalence was detected ( residents with type 1 DM vs controls ; residents with type 2 DM vs controls ) for nausea or vomiting ( 12 % vs 11 % ; 6 % vs 6 % ) , dyspepsia ( 19 % vs 21 % ; 13 % vs 17 % ) , or constipation ( 17 % vs 14 % ; 10 % vs 12 % ) . However , constipation and /or laxative use was slightly more common in residents with type 1 DM ( 27 % vs 19 % ; P<.15 ) , particularly in men , and was associated with the intake of calcium channel blockers . CONCLUSIONS In the community , the prevalence of most GI tract symptoms is similar in persons with or without DM , except for a lower prevalence of heartburn and an increased prevalence of constipation or laxative use in residents with type 1 DM , especially in men . This difference is associated with calcium channel blocker use rather than symptoms of autonomic neuropathy . In community-based practice s , physicians should not immediately assume that GI tract symptoms in patients with DM represent a complication of DM BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475 BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com CONTEXT Fractures are a major health burden in elderly institutionalized persons . Type 2 diabetes mellitus ( DM ) has a high prevalence in nursing home patients and has been associated with positive effects on bone mass in younger , community-dwelling elderly . OBJECTIVE The objective of this study was to investigate whether type 2 DM affects bone mass , bone turnover , or prospect i ve fracture rates in frail , elderly women living in nursing homes . DESIGN , SETTING , AND PARTICIPANTS This study was a prospect i ve cohort of 583 patients with type 2 DM and 1081 control ( CTR ) individuals above age 70 recruited from 95 nursing homes in Austria . Patients were enrolled and followed up by mobile study teams . MAIN OUTCOME MEASURES We performed  quantitative bone ultrasound measurements  at the calcaneus , radius , and proximal third phalanx , measurements of quadriceps strength , and biochemical parameters of mineral metabolism and bone turnover . Patients were prospect ively followed for hip and other nonvertebral fractures over 2 yr . RESULTS Patients with type 2 DM had significantly higher age- , weight- , and mobility score-adjusted calcaneal stiffness ( P < 0.0001 ) , radial speed of sound ( P < 0.005 ) , and phalangeal speed of sound ( P < 0.05 ) measurements when compared with CTRs . Mean serum PTH ( -20.7 % ) and osteocalcin levels ( -22.3 % ) were significantly lower ( both P < 0.0001 ) in patients with treated type 2 DM despite comparable low serum 25-hydroxyvitamin D levels and slightly higher adjusted total serum calcium levels compared with CTRs . Important independent determinants of bone turnover in both patient groups were PTH , creatinine clearance , alanine aminotransferase , as well as glycosylated hemoglobin levels , together accounting for 30 - 40 % of its variance . A total of 110 hip fractures occurred during the observation period , corresponding to a hip fracture rate of 3.1 % ( in CTRs ) and 3.4 % ( in type 2 DM ) per 100 patient years ; this was not significantly different for CTRs and diabetics . CONCLUSIONS Decreased PTH levels and higher levels of glycemia independently contribute to lower bone turnover in elderly nursing home patients with type 2 DM . Despite higher bone mass and lower bone turnover , hip fracture risk is comparable with women without DM Introduction : Many studies support the role of vitamin D in the pathogenesis of both types of diabetes . Pancreatic tissues express the vitamin D receptor ( VDR ) and vitamin D-binding protein ; some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose intolerance , defective insulin secretion , and sensitivity . Epidemiological links have been established between type 2 diabetes mellitus ( DM ) and hepatitis C virus ( HCV ) infection . Aim : To explore the possible therapeutic potential of pharmacologic doses of 1-α-hydroxy vitamin D therapy in improving pancreatic β-cell function in HCV seropositive hemodialysis ( HD ) patients . Patients and methods : Twenty HCV seropositive HD patients and 20 HCV seronegative patients as control group were r and omly selected from HD units .  1-α-Hydroxy vitamin D therapy was administrated in the dose ranged from 0.25 to 0.5 μg/day for 3 months  . Corrected total serum calcium , phosphorus , intact parathyroid hormone ( iPTH ) , 25-hydroxy vitamin D [ 25(OH ) vitamin D ] , 1,25-dihydroxy vitamin D , and glucoparameters [ fasting blood glucose , glycohemoglobin test ( HbA1c% ) , homeostatic model assessment (HOMA)-insulin resistance , and HOMA-β-cell function% ( B% ) ] were measured under basal conditions and after 3 months of therapy . Results : There was highly significant improvement in the concentrations of fetal bovine serum ( FBS ) , serum insulin , HbA1c% , 25(OH ) vitamin D , and HOMA-β-cell function in HCV seropositive and HCV seronegative groups after oral 1-alphacalcidiol therapy ( p < 0.001 ) . Positive correlation exists between the percentage increase in serum insulin and that in HOMA-β-cell function versus 25(OH ) vitamin D ( p < 0.021 and p < 0.027 , respectively ) in HCV negative group . Conclusion : 1-α-Hydroxy vitamin D oral therapy may improve glycemic control in HCV seropositive and HCV seronegative HD patients Objective : To determine the effects of zinc ( Zn ) supplementation on oxidative stress in persons with type 2 diabetes mellitus ( type 2 DM ) . Design : Tunisian adult subjects with HbA1c > 7.5 % were supplemented for six months with 30 mg/day of Zn as Zn gluconate or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , urinary Zn , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and glutathione peroxidase activities ( GPX ) in red blood cells , blood lipids and lipoproteins , HbA1c and fasting glucose were measured at the beginning of the study and after three and six months . Results : At the beginning of the study , more than 30 % of the subjects exhibited plasma Zn values less than the normal minimum of 10.7 μmol/L , whereas levels of plasma Cu and antioxidant RBC Cu-Zn SOD and GPx enzyme activities were in the normal ranges . Oxidative stress , monitored by plasma TBARS , was increased in individuals with diabetes compared with healthy Tunisian subjects ( 3.32 ± 0.05 μmol/L vs. 2.08 ± 0.04 μmol/L ) and an inverse correlation was found between Zn plasma levels and plasma TBARS . After three and six months of Zn supplementation , all of the subjects exhibited plasma Zn values greater than 10.7 μmol/L. There was a decrease of plasma TBARS in Zn supplemented group after six months ( 15 % ) with no significant changes in the placebo group . Supplementation did not alter significantly HbA1c nor glucose homeostasis . No adverse effects of Zn supplementation were observed on Cu status or HDL cholesterol . Conclusions : These data suggest the potential beneficial antioxidant effects of Zn supplementation in persons with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in persons with diabetes OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes .  RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes .  Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from supplements . A combined daily intake of > 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of < 600 mg and 400 IU calcium and vitamin D , respectively . CONCLUSIONS The results of this large prospect i ve study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes BACKGROUND Oral amino acid intake reduces plasma glucose in Streptozotocin-induced diabetic rats . This study examined the effect of oral amino acid supplementation in patients with type 2 diabetes mellitus ( DM ) . MATERIAL / METHODS A double blind pilot clinical trial was conducted for a period of 2 months on 77 subjects with type 2 DM . Subjects of both sexes , ages 30 - 60 , were included in the trial . All were receiving oral antidiabetic tablets . They were divided into groups on the basis of oral supplementation : ( A ) lysine , ( B ) essential amino acids , ( C ) amino acids and vitamins ( fat and water-soluble ) , and ( D ) calcium phosphate ( control ) . The subjects were periodically examined for fasting and post-pr and ial plasma glucose , fasting and post-pr and ial immunoreactive insulin , plasma amino acids , glycosylated haemoglobin ( HbA1c ) , proteins and albumin in serum , urea and creatinine in plasma and sugar , and proteins and ketones in urine . RESULTS The results revealed a significant decrease in PP plasma glucose ( P<0.05 ) in group B when compared to groups C and D after 45 days . Plasma Arginine was increased in group C from 3.84 to 9.24 mg/dl . There were no statistically significant changes seen in other parameters between groups and visits . CONCLUSIONS Oral supplementation with amino acids for patients with type 2 DM appears to decrease PP plasma glucose without any change in plasma insulin levels , perhaps due to improved insulin sensitivity . However , the long term effects of amino acids need further study Background / Aims Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels , glucose intolerance/insulin resistance ( IR ) , and cardiovascular disease . However , few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk , such as IR and arterial stiffness , in diabetes . We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients , including metabolic parameters , IR , and arterial stiffness . Methods We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes . We excluded patients who were taking vitamin D or calcium supplements .  We r and omized participants into the vitamin D group ( cholecalciferol 2,000 IU/day + calcium 200 mg/day , n = 40 ) or the placebo group ( calcium 200 mg/day , n = 41 ) . We compared their IR ( homeostasis model of assessment [HOMA]-IR ) and arterial stiffness ( brachial-ankle pulse wave velocity and radial augmentation index ) before and after 24 weeks of intervention . Results The baseline characteristics of the two groups were similar . A total of 62 participants ( placebo , 30 ; vitamin D , 32 ) completed the study protocol . At the end of the study period , the 25-hydroxyvitamin D [ 25(OH)D ] levels were significantly higher in the vitamin D group than in the placebo group ( 35.4 ± 8.5 ng/mL vs. 18.4 ± 7.3 ng/mL , p < 0.001 ) . There was no difference in HOMA-IR or changes in arterial stiffness  ( placebo , 21 , vitamin D , 24 ) between the groups . Conclusions Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels . However , we identified no beneficial effects on cardiovascular risk in type 2 diabetes , including IR and arterial stiffness Objective — Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events . However , these studies did not address possible benefit to subgroups with increased oxidative stress . Haptoglobin ( Hp ) , a major antioxidant protein , is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus ( DM ) . The Hp gene is polymorphic with 2 common alleles , 1 and 2 . The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product . We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2 - 2 genotype , a subgroup that comprises 2 % to 3 % of the general population . Methods and Results —1434 DM individuals ≥55 years of age with the Hp 2 - 2 genotype were r and omized to vitamin E ( 400 U/d ) or placebo . The primary composite outcome was myocardial infa rct ion , stroke , and cardiovascular death . At the first evaluation of events , 18 months after initiating the study , the primary outcome was significantly reduced in individuals receiving vitamin E ( 2.2 % ) compared with placebo ( 4.7 % ; P=0.01 ) and led to early termination of the study . Conclusions —Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2 - 2 genotype ( Clinical Trials.gov NCT00220831 ) Low vitamin K status is associated with low BMD and increased fracture risk . Additionally , a specific menaquinone , menatetrenone ( MK4 ) , may reduce fracture risk . However , whether vitamin K plays a role in the skeletal health of North American women remains unclear . Moreover , various K vitamers ( e.g. , phylloquinone and MK4 ) may have differing skeletal effects . The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic , postmenopausal , North American women . In this double-blind , placebo-controlled study , 381 postmenopausal women received phylloquinone  ( 1 mg daily ) , MK4 ( 45 mg daily ) , or placebo for 12 mo . All participants received daily calcium and vitamin D(3 ) supplementation . Serum bone-specific alkaline phosphatase ( BSALP ) and n-telopeptide of type 1 collagen ( NTX ) were measured at baseline and 1 , 3 , 6 , and 12 mo . Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo . At baseline , the three treatment groups did not differ in demographics or study endpoints . Compliance with calcium , phylloquinone , and MK4  treatment was 93 % , 93 % , and 87 % , respectively . Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX . No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed . This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy , postmenopausal , North American women receiving calcium and vitamin D supplementation The pathology of type 2 diabetes mellitus ( DM ) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation . Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease . The present r and omized , double-blind , placebo-controlled , 12-week trial was design ed to investigate the effects of zinc ( 40 mg/day ) and α-linolenic acid ( ALA ; 2 g/day flaxseed oil ) supplementation on markers of inflammation [ interleukin (IL)-1β , IL-6 , tumor necrosis factor (TNF)-α , C-reactive protein ( CRP ) ] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM . No significant effects of  zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression . Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA ( P=.007 and P=.009 , respectively ) . An impact of zinc treatment on zinc transporter gene expression was found ; ZnT5 was positively correlated with Zip3 mRNA ( P<.001 ) only in participants receiving zinc , while zinc supplementation abolished the relationship between ZnT5 and Zip10 . IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5 , ZnT7 , Zip1 , Zip7 and Zip10 mRNA cluster ( P<.001 and P=.031 , respectively ) . Fold change in the expression of metallothionein mRNA was predicted by TNF-α ( P=.022 ) . Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM BACKGROUND Chronic low- grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes . Therefore , reducing inflammation can be beneficial in prevention of diabetes complications . OBJECTIVES To investigate the association between insulin resistance and inflammatory markers , and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients . METHODS In this double-blind r and omized placebo-controlled trial , 70 participants with type-2 diabetes were r and omly divided to two groups . One group received two capsules of Calcitriol ( 0.25 μg 1,25-dihydroxy cholecalciferol per each capsule ) per day . The second group received placebo tablets . At the beginning of the study , we assessed insulin resistance and its relation to inflammatory profile . Serum high sensitive C-reactive protein ( hs CRP ) , interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial . RESULTS Mean calcium , phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL , 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL , respectively . IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers . At the end of the 12-week supplementation trial , no significant difference was seen in serum levels of hsCRP , IL-6 and IL-18 between the two groups , while these values were adjusted for baseline values . CONCLUSION Inflammation was associated with insulin resistance in diabetic patients . No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP , IL-6 and IL-18 detected Background : A prospect i ve , nonblinded and nonr and omized controlled trial was conducted to test the hypothesis that vitamin D supplementation would improve glycemic control in patients with type 1 diabetes mellitus who have vitamin D deficiency . Patients and Methods :0 Eighty patients with type 1 diabetes mellitus who had 25-hydroxyvitamin D levels less than 50 nmol/L were assigned to receive 4000 IU of vitamin D3 . Calcium supplements were provided to ensure a total calcium intake of 1200 mg/d . Glycosylated hemoglobin and 25-hydroxyvitamin D levels were measured at baseline and at 12 weeks . Results : There was a significant difference in mean ( SD ) glycosylated hemoglobin level ( % ) between the groups that achieved 25-hydroxyvitamin D levels of < 35.4 nmol/L , 35.4 - 51 nmol/L and > 51 nmol/L at 12 weeks ( P=.02 ) . There was a significant difference in glycosylated hemoglobin change from baseline between the groups that achieved 25-hydroxyvitamin D levels of < 35.4 nmol/L , 35.4 - 51 nmol/L and > 51 nmol/L at 12 weeks ( P=.04 ) . There was a significant difference in 25-hydroxyvitamin D level between the groups that achieved glycosylated hemoglobin levels of < 7.8 , 7.8 - 9.9 and > 9.9 at 12 weeks ( P=.001 ) . Patients were more likely to achieve lower glycosylated hemoglobin levels at 12 weeks if they had higher 25-hydroxyvitamin D levels at 12 weeks ( r=-0.4 , P=.001 ) . Conclusions : There was an observed effect of vitamin D supplementation on glycemic control in vitamin D-replete , type 1 diabetes mellitus patients . Further studies are needed to determine if these findings are applicable
Evidence from trials with vitamin D and /or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in population s at high risk ( i.e. glucose intolerance ) .
Vitamin D and calcium insufficiency may negatively influence glycemia , whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism
CONTEXT Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus ( type 2 DM ) .