Vitamin D and Diabetes:
Subject: Vitamin D supplementation lowers the risk of developing Type I diabetes and may also help prevent and treat Type II diabetes.
Vitamin D can play a role in preventing and treating both types of diabetes. Recall that there are two distinct forms of diabetes. The names have changed over the years. We used to differentiate them by age of onset: Juvenile versus Adult onset. Then more simply as Type I versus Type II diabetes. More recently, for practical purposes, the distinction has been whether the patient needs insulin: Insulin Dependent Diabetes Mellitus (IDDM) versus Non Insulin Dependent Diabetes Mellitus (NIDDM). For this discussion I am going to take the middle ground and use the Type I and II designation. This designation differentiates the two forms of the disease.
Current medical understanding is that Type I diabetes, what used to be called Juvenile onset diabetes mellitus, is caused by an autoimmune process; the body's immune system attacks the insulin producing cells in the pancreas and destroys them. The pancreas is unable to produce insulin and the disease needs to be treated with insulin injections.
The hallmark of Type II diabetes is insulin resistance. The cells of the body no longer respond with the same degree of sensitivity as normal cells. It takes greater and greater amounts of insulin to stimulate the cells to utilize sugar. This form of diabetes is treated two ways. First, insulin levels are increased either by oral drugs to stimulate the pancreas to make more insulin or by giving insulin injections or even both methods together. Second, drugs are used to decrease insulin resistance. The most common one is Metformin. Chromium, brewer's yeast, vitamin E and biotin are used by natural minded practitioners to do the same thing, decrease insulin resistance.
Vitamin D appears to be useful in a number of different ways in preventing and treating diabetes. Let's talk about Type I diabetes first.
The chance of developing Type I diabetes varies with where you live. The closer you live to the equator, the lower your risk. The further from the equator, and the less ultraviolet exposure you get, the higher your risk. The more sunlight and ultraviolet exposure you get, the more Vitamin D you make. A study in Australia showed a 300% increase in diabetes moving from Northern Australia (which is closer to the equator and sunnier) to Southern Australia . [i] The same association with diabetes and latitude is seen in European countries: the further north you live the higher the incidence of Type I diabetes. [ii]
Remember that Type 1 diabetes is caused by autoimmune inflammatory destruction of the pancreatic beta-cells. Vitamin D seems to have both an anti-inflammatory effect and also suppresses auto-immune activity. So researchers have looked at Vitamin D in diabetes. Supplementation with D has been shown to prevent diabetes and help control it in animal models. In a human clinical trial researchers gave infants and young children 2000 iu of Vitamin D per day. As these kids grew up they had strikingly lower rates of type I diabetes develop. Taking the vitamin D reduced their risk by 80%. Children in this study who had been diagnosed with Rickets', a disease of Vitamin D deficiency, prior to starting the study, were three times as likely to develop diabetes than the controls who had no vitamin D supplementation. [iii]
There are several studies like this one in which cod liver oil was given and showed similar results protecting against diabetes. [iv] Just taking cod liver oil during pregnancy reduces risk of type I diabets in offspring. [v] Cod liver oil is the traditional source of vitamin D but it also a source of beneficial fatty acids. As a result there is some debate whether it is the vitamin D or the omega-3 fats in cod liver oil providing the benefit. The repeated benefit seen with Vitamin D in various different settings seems to argue in favor of it, although there is no reason that it can't be both the oil and the vitamin acting. [vi]
There is one study that showed cod liver oil was of benefit but not Vitamin D. It was unclear which form of vitamin D and how much was used in this negative study. [vii] From my reading it appears that the D-3 form is the one that helps and the more common D-2 form may not be beneficial. More details on this on another day.
A study giving high doses of Vitamin D early in life decreased the rates of schizophrenia in boys. [viii] But not girls. That's not really relevant to this discussion but it still is interesting. Fish oils have been widely touted for treating mental disorders. Perhaps it's the vitamin D in them and not the fatty acids.
These studies used fairly high doses of Vitamin D. The benefit of using lower doses of has not been proven. [ix]
Now let's talk about Type II diabetes, the one with insulin resistance. Older studies show Vitamin D improves glucose tolerance and insulin secretion in rats [x] and rabbits. [xi] When researchers switched to trying vitamin D on human diabetics, the effect was less pronounced. The benefit was more clearly seen in diabetics that were recently diagnosed with the disease. [xii]
Vitamin D may be important much earlier on. Low Vitamin D levels are associated with insulin resistance and beta cell dysfunction in diabetics and also in apparently healthy young adults. When adults undergo a two hour test of glucose levels following a large dose of glucose, those who have higher Vitamin D levels have much better test results. [xiii] Similar results are seen in elderly men. Vitamin D levels can be used to predict results on a glucose tolerance test. [xiv]
When Vitamin D deficiencies are chemically induced in human subjects, it raises blood sugar levels and decreases insulin sensitivity. [xv] Vitamin D-3 supplementation increases insulin secretion in non insulin dependent diabetics. [xvi]
The drug often used to treat Type II diabetics, Metformin may improve insulin sensitivity by 13%. Some reports say vitamin D can increase sensitivity by 60%. [xvii] A recent study using just 1332 iu/day of Vitamin D in women with type 2 diabetes for 30 days showed a 21% increase in insulin sensitivity. [xviii] The benefits of Vitamin D occur slowly; one would not expect to see full benefit for six or more months.
Put all of these facts together and it is time to change our protocols. All diabetics should be tested for Vitamin D levels and supplemented if inadequate. Pregnant women should take fish oil supplements and extra vitamin D. Supplementation for children especially in the first year of life and in northern latitudes should be considered.
[i] Environ Health Perspect. 2003 Apr;111(4):518-23.
Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia : latitude, regional ultraviolet radiation, and disease prevalence.
Staples JA, Ponsonby AL, Lim LL, McMichael AJ.
National Center for Epidemiology and Population Health, The Australian National University , Canberra , Australian Capital Territory , Australia . firstname.lastname@example.org
The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77; p = 0.026) and decreasing regional annual ambient UVR (r= -0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72; p = 0.046), although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia , and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are required.
PMID: 12676609 [PubMed - indexed for MEDLINE]
[ii] Toxicology. 2002 Dec 27;181-182:71-8.
Ultraviolet radiation and autoimmune disease: insights from epidemiological research.
Ponsonby AL, McMichael A, van der Mei I.
National Centre for Epidemiology and Population Health, The Australian National University , Canberra ACT 0200, Australia . email@example.com
This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America . Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the individual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed.
PMID: 12505287 [PubMed - indexed for MEDLINE]
[iii] Lancet. 2001 Nov 3;358(9292):1500-3.
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.
Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM.
Department of Paediatric Epidemiology and Biostatistics, Institute of Child Health , WC1N 1EH , London , UK . firstname.lastname@example.org
BACKGROUND: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes in animals. Our aim was to ascertain whether or not vitamin D supplementation or deficiency in infancy could affect development of type 1 diabetes. METHODS: A birth-cohort study was done, in which all pregnant women (n=12055) in Oulu and Lapland , northern Finland , who were due to give birth in 1966 were enrolled. Data was collected in the first year of life about frequency and dose of vitamin D supplementation and presence of suspected rickets. Our primary outcome measure was diagnosis of type 1 diabetes by end of December, 1997. FINDINGS: 12058 of 12231 represented live births, and 10821 (91% of those alive) children were followed-up at age 1 year. Of the 10366 children included in analyses, 81 were diagnosed with diabetes during the study. Vitamin D supplementation was associated with a decreased frequency of type 1 diabetes when adjusted for neonatal, anthropometric, and social characteristics (rate ratio [RR] for regular vs no supplementation 0.12, 95% CI 0.03-0.51, and irregular vs no supplementation 0.16, 0.04-0.74. Children who regularly took the recommended dose of vitamin D (2000 IU daily) had a RR of 0.22 (0.05-0.89) compared with those who regularly received less than the recommended amount. Children suspected of having rickets during the first year of life had a RR of 3.0 (1.0-9.0) compared with those without such a suspicion. INTERPRETATION: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.
PMID: 11705562 [PubMed - indexed for MEDLINE]
[iv] Lancet. 2001 Nov 3;358(9292):1500-3.
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.
Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM.
[v] Diabetologia. 2000 Sep;43(9):1093-8.
Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring.
Stene LC, Ulriksen J, Magnus P, Joner G.
Section of Epidemiology, National Institute of Public Health, Oslo , Norway .
AIMS/HYPOTHESIS: To test whether cod liver oil or vitamin D supplements either taken by the mother during pregnancy or by the child in the first year of life is associated with lower risk of Type I (insulin-dependent) diabetes mellitus in children. METHODS: We carried out a population-based case control study in Vest-Agder county of Norway , evaluating the use of supplements by a mailed questionnaire. We received responses from 85 diabetic subjects and 1,071 control subjects. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression analyses. RESULTS: When mothers took cod liver oil during pregnancy their offspring had a lower risk of diabetes. The unadjusted OR was 0.30, 95% CI: (0.12 to 0.75), p = 0.01. This association changed very little and was still significant after adjusting for age, sex, breastfeeding and maternal education. Mothers taking multivitamin supplements during pregnancy [adjusted OR= 1.11, 95% CI: (0.69 to 1.77)], infants taking cod liver oil in the first year of life [adjusted OR = 0.82, 95 % CI: (0.47 to 1.42) and the use of other vitamin D supplements in the first year of life [adjusted OR = 1.27, 95 % CI: (0.70 to 2.31)] was not [corrected] significantly associated with the risk of diabetes. CONCLUSION/INTERPRETATION: We found that cod liver oil taken during pregnancy was associated with reduced risk of Type I diabetes in the offspring. This suggests that vitamin D or the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the cod liver oil, or both, have a protective effect against Type I diabetes.
PMID: 11043854 [PubMed - indexed for MEDLINE]
[vi] Diabetologia. 1999 Jan;42(1):51-4.
Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group.
[No authors listed]
The initiation of the immunopathogenetic process that can lead to Type I (insulin-dependent) diabetes mellitus in childhood probably occurs early in life. Studies in vitro have shown that vitamin D3 is immunosuppressive or immunomodulating and studies in experimental models of autoimmunity, including one for autoimmune diabetes, have shown vitamin D to be protective. Seven centres in Europe with access to population-based and validated case registers of insulin-dependent diabetes patients participated in a case-control study focusing on early exposures and risk of Type I diabetes. Altogether data from 820 patients and 2335 control subjects corresponding to 85% of eligible patients and 76% of eligible control subjects were analysed. Questions focused on perinatal events and early eating habits including vitamin D supplementation. The frequency of vitamin D supplementation in different countries varied from 47 to 97% among control subjects. Vitamin D supplementation was associated with a decreased risk of Type I diabetes without indication of heterogeneity. The Mantel-Haenszel combined odds ratio was 0.67 (95% confidence limits: 0.53, 0.86). Adjustment for the possible confounders: a low birth weight, a short duration of breast feeding, old maternal age and study centre in logistic regression analysis did not affect the significant protective effect of vitamin D. In conclusion, this large multicentre trial covering many different European settings consistently showed a protective effect of vitamin D supplementation in infancy. The findings indicate that activated vitamin D might contribute to immune modulation and thereby protect or arrest an ongoing immune process initiated in susceptible people by early environmental exposures.
PMID: 10027578 [PubMed - indexed for MEDLINE]
[vii] Am J Clin Nutr. 2003 Dec;78(6):1128-34.
Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study.
Stene LC, Joner G; Norwegian Childhood Diabetes Study Group.
Diabetes Research Centre, Aker and Ulleval University Hospitals , Department of Paediatrics, Ulleval University Hospital , Oslo , Norway . email@example.com
BACKGROUND: In Norway , cod liver oil is an important source of dietary vitamin D and the long-chain n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, all of which have biological properties of potential relevance for the prevention of type 1 diabetes. OBJECTIVE: The main objective was to investigate whether the use of dietary cod liver oil or other vitamin D supplements, either by the mother during pregnancy or by the child during the first year of life, is associated with a lower risk of type 1 diabetes among children. DESIGN: We designed a nationwide case-control study in Norway with 545 cases of childhood-onset type 1 diabetes and 1668 population control subjects. Families were contacted by mail, and they completed a questionnaire on the frequency of use of cod liver oil and other vitamin D supplements and other relevant factors. RESULTS: Use of cod liver oil in the first year of life was associated with a significantly lower risk of type 1 diabetes (adjusted odds ratio: 0.74; 95% CI: 0.56, 0.99). Use of other vitamin D supplements during the first year of life and maternal use of cod liver oil or other vitamin D supplements during pregnancy were not associated with type 1 diabetes. CONCLUSION: Cod liver oil may reduce the risk of type 1 diabetes, perhaps through the antiinflammatory effects of long-chain n-3 fatty acids.
PMID: 14668274 [PubMed - indexed for MEDLINE]
[viii] Schizophr Res. 2004 Apr 1;67(2-3):237-45.
Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study.
McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Jarvelin MR, Chant D, Isohanni M.
Department of Psychiatry, University of Cambridge , Cambridge , UK . firstname.lastname@example.org
OBJECTIVE: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. METHOD: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n=9,114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. RESULTS: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR)=0.08, 95% CI 0.01-0.95; RR=0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. CONCLUSION: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia.
PMID: 14984883 [PubMed - indexed for MEDLINE
[ix] Nutr Rev. 2002 Apr;60(4):118-21.
Can vitamin D supplementation in infancy prevent type 1 diabetes?
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston , MA 02111 , USA .
Several recent European studies suggested that supplementing infants with vitamin D during their first year might prevent type 1 diabetes. A dose of 50 microg/day was associated with decreased diabetes risk in Finland , but the effectiveness of lower doses was not examined. The recommended dietary intake of vitamin D for U.S. infants is 5 microg/day and the tolerable upper level is 25 microg/day. There is no evidence that intakes between 5 and 25 microg/day would reduce diabetes incidence, but it would seem prudent to ensure that infants reach at least the lower end of this range.
PMID: 12002683 [PubMed - indexed for MEDLINE]
[x] Endocrinology. 1986 Jul;119(1):84-90
Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo .
Cade C, Norman AW.
It has previously been shown in this laboratory that vitamin D3 is essential for normal insulin secretion from the perfused rat pancreas. In this present study, the influence of vitamin D status on insulin secretion in vivo was investigated. Intravenous glucose tolerance tests were performed on conscious vitamin D-deficient rats (-D), vitamin D-replete rats fed ad libitum (+D AL), and vitamin D-replete rats pair fed to the D-deficient animals (+D PF). Vitamin D deficiency, easily recognizable by low daily dietary intake and depressed plasma calcium levels, was found to impair plasma glucose clearance as characterized by an elevated KG value (representing a function of the area beneath the tolerance curve). KG values for the +D AL, +D PF, and -D groups were 504 +/- 15, 480 +/- 46, and 641 +/- 28, respectively. The increase in KG corresponded to a significant reduction in glucose-mediated insulin secretion as compared to the +D animals. This difference appeared not to be related to the increase caloric intake associated with vitamin D repletion, since +D rats which had been pair fed to the -D animals also exhibited restored plasma insulin levels in response to glucose. Plasma phosphorus concentrations were comparable in all three groups, and thus this parameter is also unlikely to be a contributory factor in the observed phenomenon. Additional experiments were conducted to evaluate the involvement of hypocalcemia in the observed impaired glucose tolerance. Normalization of plasma calcium levels (from 4.8 mg/100 ml to 9.6/100 ml) of the -D rats, by dietary calcium and phosphorus manipulation, failed to improve glucose clearance (KG for -D normocalcemic rats = 639 +/- 61) or insulin secretion. These results support the concept that vitamin D plays a physiological role in insulin secretion, acting, at least in part, independently of nutritional factors and the prevailing plasma calcium and phosphorus concentrations.
PMID: 3013599 [PubMed - indexed for MEDLINE]
[xi] Endocrinology. 1984 Jul;115(1):191-7.
Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit.
Nyomba BL, Bouillon R, De Moor P.
The influence of vitamin D status on insulin secretion and glucose tolerance was studied by a longitudinal design in the rabbit. Intravenous glucose tolerance tests were performed in Dutch rabbits (n = 12) before and after nutritional vitamin D deficiency, characterized by an absence of circulating 25-hydroxyvitamin D3, a 50% decrease in 1,25-dihydroxyvitamin D3, and a 16% decrease in serum calcium concentrations. Glucose-induced insulin secretion was reduced by 41% as early as 2 months after the start of the vitamin D-deficient diet and was associated with an impairment of glucose tolerance. An iv calcium infusion restored the serum calcium concentration of the vitamin D-deficient rabbits (n = 5), but did not improve glucose-mediated insulin secretion. When these animals received a single ip injection of 100 ng 1,25-dihydroxyvitamin D3 10 h before the glucose test, their insulin responses significantly increased. Supplementation with 25-hydroxyvitamin D3 for 2 weeks in another group of rabbits (n = 4) resulted in marked improvement in glucose-stimulated insulin release and glucose tolerance. These results show that vitamin D affects glucose-induced insulin secretion by a mechanism that involves more than its regulating action on serum calcium concentration.
PMID: 6376069 [PubMed - indexed for MEDLINE]
[xii] Am J Clin Nutr. 1994 May;59(5):1083-7.
Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus.
Orwoll E, Riddle M, Prince M.
Bone and Mineral Research Unit, Department of Veterans' Affairs Medical Center , Portland , OR 97207 .
Vitamin D has been shown to increase insulin release from pancreatic islet cells in vitro, and to improve insulin secretion in vitamin D-deficient animals. Few attempts have been made to evaluate this issue directly in humans. We studied 35 otherwise healthy diabetic subjects in the early spring at the seasonal nadir of 25-hydroxyvitamin D [25(OH)D] concentrations (mean 35 +/- 7 nmol/L). Fasting glucose, insulin, C-peptide, and glucagon concentrations, and their responses to Sustacal stimulation were not related to indexes of mineral metabolism. In 20 subjects, a double-blinded, placebo-controlled, crossover trials of 1,25-dihydroxyvitamin D[1,25](OH)2D] treatment (1 micrograms/d for 4 d) had no effect on fasting or stimulated glucose, insulin, C-peptide, or glucagon concentrations. However, insulin and C-peptide responses to Sustacal after 1,25(OH)2D treatment were related to duration of diabetes (r2 = 0.28, P = 0.052 and r2 = 0.25, P = 0.002, respectively) in that short duration correlated with improvement after 1,25(OH)2D treatment. Hence, vitamin D nutrition, or 1,25(OH)2D therapy, had no major effect on glucose homeostasis in non-insulin-dependent diabetes mellitus.
Controlled Clinical Trial
PMID: 8172095 [PubMed - indexed for MEDLINE]
[xiii] Am J Clin Nutr. 2004 May;79(5):820-5.
Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction.
Chiu KC, Chu A, Go VL, Saad MF.
Division of Clinical Epidemiology and Preventive Medicine, Department of Medicine, University of California-Los Angeles School of Medicine, 924 Westwood Boulevard, Los Angeles, CA 90024, USA. email@example.com
BACKGROUND: Although the role of vitamin D in type 2 diabetes is well recognized, its relation to glucose metabolism is not well studied. OBJECTIVE: We investigated the relation of 25-hydroxyvitamin D [25(OH)D] concentrations to insulin sensitivity and beta cell function. DESIGN: We enrolled 126 healthy, glucose-tolerant subjects living in California . Insulin sensitivity index (ISI) and first- and second-phase insulin responses (1stIR and 2ndIR) were assessed by using a hyperglycemic clamp. RESULTS: Univariate regression analyses showed that 25(OH)D concentration was positively correlated with ISI (P < 0.0001) and negatively correlated with 1stIR (P = 0.0045) and 2ndIR (P < 0.0001). Multiple regression analyses confirmed an independent correlation between 25(OH)D concentration and ISI (P = 0.0007). No independent correlation was observed between 25(OH)D concentration and 1stIR or 2ndIR. However, an independent negative relation of 25(OH)D concentration with plasma glucose concentration was observed at fasting (P = 0.0258), 60 min (P = 0.0011), 90 min (P = 0.0011), and 120 min (P = 0.0007) during the oral-glucose-tolerance test. Subjects with hypovitaminosis D (<20 ng/mL) had a greater prevalence of components of metabolic syndrome than did subjects without hypovitaminosis D (30% compared with 11%; P = 0.0076). CONCLUSIONS: The data show a positive correlation of 25(OH)D concentration with insulin sensitivity and a negative effect of hypovitaminosis D on beta cell function. Subjects with hypovitaminosis D are at higher risk of insulin resistance and the metabolic syndrome. Further studies are required to explore the underlying mechanisms.
PMID: 15113720 [PubMed - indexed for MEDLINE]
[xiv] Diabetologia. 1997 Mar;40(3):344-7.
Vitamin D, glucose tolerance and insulinaemia in elderly men.
Baynes KC, Boucher BJ, Feskens EJ, Kromhout D.
Cellular Mechanisms Research Group, St. Bartholomew's, Royal London School of Medicine and Dentistry, Whitechapel, London, UK.
Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospective population-based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus. Of the men aged 70-88 years examined between March and May 1990, 39% were vitamin D depleted. After adjustment for confounding by age, BMI, physical activity, month of sampling, cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test (OGTT) were inversely associated with the serum concentration of 25-OH vitamin D (r = -0.23, p < 0.01; r = -0.26, p < 0.01, respectively). After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D may be a significant risk factor for glucose intolerance.
PMID: 9084975 [PubMed - indexed for MEDLINE]
[xv] Diabetologia. 1986 Jan;29(1):34-8.
Pancreatic secretion in man with subclinical vitamin D deficiency.
Nyomba BL, Auwerx J, Bormans V, Peeters TL, Pelemans W, Reynaert J, Bouillon R, Vantrappen G, De Moor P.
The effects of subclinical vitamin D deficiency and vitamin D supplementation on oral glucose tolerance and secretion of pancreatic hormones were studied in 10 diphenylhydantoin-treated epileptic patients and 15 geriatric patients. Their mean serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 decreased markedly, but returned to normal within 2 weeks of oral supplementation with 25-hydroxyvitamin D3. The serum concentration of ionized calcium was within the normal range before treatment, and remained unchanged. Serum parathyroid hormone was increased during vitamin D deficiency, but decreased significantly (p less than 0.05) afterwards. In vitamin D-deficient epileptic and geriatric patients, the 2- and 3-h insulin levels after glucose ingestion were increased when compared with control values, and glucagon secretion was not suppressed by glucose. Oral glucose tolerance of both groups of patients did not change after 25-hydroxyvitamin D3 supplementation. Insulin secretion remained unchanged in geriatric patients, but was reduced to normal values in epileptic patients. Glucagon suppressibility by glucose was partly restored after vitamin D supplementation in epileptic patients but not in geriatric patients. In contrast to that observed in severely vitamin D-deficient rats or rabbits, correction of subclinical vitamin D deficiency failed to enhance insulin secretion or to improve glucose tolerance in man.
PMID: 3754230 [PubMed - indexed for MEDLINE]
[xvi] Bone Miner. 1986 Jun;1(3):187-92.
Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus.
Inomata S, Kadowaki S, Yamatani T, Fukase M, Fujita T.
Department of Internal Medicine, Kobe Teishin Hospital , Japan .
Fourteen non-insulin-dependent diabetic subjects were placed on a balanced diet for 2-3 weeks followed by the same balanced diet alone (group I: control, n = 7) or daily administration of 1 alpha (OH)-vitamin D3 (1 alpha (OH)D3) (group II: 2 micrograms/day, n = 7) additionally for the next 3 weeks. A 75 g oral glucose loading test was conducted before and after the experiment and the plasma insulin response was compared along with the metabolic parameters including serum calcium, phosphorus and serum lipids. The following results were obtained. (1) Total insulin secretion in response to 75 g glucose loading was significantly increased in group II (16.3 +/- 3.9 microU/2 h/ml versus 22.7 +/- 4.9 microU/2 h/ml; P less than 0.05), though no difference was demonstrated in group I. (2) Mean serum calcium level was significantly increased from 9.4 +/- 0.1 mg/dl to 9.6 +/- 0.1 mg/dl (P less than 0.05) and serum free fatty acid level was decreased from 0.80 +/- 0.07 mEq/l to 0.53 +/- 0.07 mEq/l (P less than 0.05) in group II, but not in group I. (3) However, there was no direct correlation between total insulin secretion during a 75 g oral glucose loading test and serum calcium or free fatty acid level. The findings that 1 alpha (OH)D3 enhances insulin secretion and reduces the levels of serum free fatty acid in non-insulin-dependent diabetics provide us with the possibility that vitamin D may play some role in the regulation of insulin secretion.
PMID: 3334207 [PubMed - indexed for MEDLINE]
[xvii] Postgrad Med J. 1994 Jun;70(824):440-3.
Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D .
Kumar S, Davies M, Zakaria Y, Mawer EB, Gordon C, Olukoga AO, Boulton AJ.
Department of Medicine, Manchester Royal Infirmary , UK .
Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism.
PMID: 8029165 [PubMed - indexed for MEDLINE]
[xviii] Int J Clin Pract. 2003 May;57(4):258-61.
The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.
Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R.
Department of Endocrinology, University Hospital , 6 Damjan Gruev str, 1303 Sofia , Bulgaria .
The aim of this study was to evaluate the effect of vitamin D3 supplementation on insulin secretion and insulin resistance. Ten females with type 2 diabetes being treated with oral hypoglycaemic agents and with normal serum and urine calcium levels were enrolled in the study. The study was conducted in March, when levels of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases of insulin secretion were studied during IVGTT. Peripheral insulin resistance was measured. A group of 17 age- and BMI-matched females with normal glucose tolerance served as a control group. The diabetic patients were treated with cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month of treatment with vitamin D3, the plasma 25(OH)D level increased by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS increased significantly by 34.3%, while the change in SPIS of 20.4% was not significant (p > 0.8). We found a significant correlation between the change in FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p < 0.018). The results showed a decrease of 21.4% in insulin resistance after one month, but the change was not significant. Bearing in mind that the main defects in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at least partly contribute to the impairment of insulin secretion and probably of insulin action. Our results suggest that vitamin D3 supplementation could be an element in the complex treatment of type 2 diabetes mellitus during the winter.
PMID: 12800453 [PubMed - indexed for MEDLINE]