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| Does Hepatic Dysfunction Worsen Glucose Homeostasis by Impairing
Vitamin D Metabolism? |
| Benjamin U Nwosu* |
| Division of Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N Worcester, MA 01655, USA |
| *Corresponding author: |
Dr. Benjamin U Nwosu
MD, Assistant Professor, Division
of Endocrinology
Department of Pediatrics
University of Massachusetts Medical
School
55 Lake Avenue N Worcester, MA 01655, USA
Tel: 508-334-7872
Fax: 508-856-4287
E-mail: Benjamin.Nwosu@umassmemorial.org |
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| Received February 28, 2012; Accepted February 28, 2012; Published March 05,
2012 |
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| Citation: Nwosu BU (2012) Does Hepatic Dysfunction Worsen Glucose
Homeostasis by Impairing Vitamin D Metabolism? Vitamin Trace Element 1:e109.
doi:10.4172/vte.1000e109 |
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| Copyright: © 2012 Nwosu BU. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited. |
| |
| The Management of diabetes mellitus (DM) remains an enigma
even though the symptoms of the disease had been described more
than 3000 years ago. This is because the central therapeutic goal of
DM therapy, euglycemia, is influenced by complex physiologic and
pathologic processes, some of which are clearly understood, while
others are less clear. Suboptimal glycemic control is a recognized
risk factor for acute and chronic complications of diabetes including
microvascular and macrovascular diseases [1-3]. The central question
for this editorial is whether mild hepatic dysfunction could impair
vitamin D metabolism and secondarily lead to sub-optimal glycemic
control. |
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| Poor glycemic control is a growing problem in patients with type 1
(T1DM) or type 2 diabetes (T2DM) [4] despite improvements in insulin
formulation, delivery and adjunctive therapies [5]. A high proportion
of youth with diabetes had elevated hemoglobin A1c (HbA1c) values,
with 17% with TIDM, and 27% of those with T2DM showing poor
control, defined as HbA1c ≥ 9.5% [4]. |
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| Nonalcoholic fatty liver disease (NAFLD) is the most common
form of liver dysfunction in children [6]. Even though its prevalence is
rising in parallel with the prevalence of childhood obesity [7], its role
in poor glycemic control in diabetes is unknown. NAFLD represents
a spectrum of conditions characterized by macrovesicular hepatic
steatosis and little or no exposure to alcohol [7]. The hepatic pathology
encompasses a range from isolated fatty infiltration to steatohepatitis,
advanced fibrosis, and cirrhosis [6]. NAFLD is the leading cause of
elevated liver enzymes in obese youth [8]. Several studies have reported
an association between liver dysfunction and low vitamin D levels
[9,10], as well as liver dysfunction and poor glycemic control [11], but
not all three disorders acting in concert. |
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| A crucial step in the metabolism of vitamin D, the hydroxylation
of pre-vitamin D at the 25 position, occurs in the liver. The role of
NAFLD on this critical step in vitamin D metabolism in children and
adolescents with diabetes has not been fully studied. Equally, the effects
of the resultant vitamin D deficiency on glycemic control in these
patients have also not been well described. |
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| The role of vitamin D on glycemic control has not been fully
studied. A study in healthy adults with normal glucose tolerance using
the hyperglycemic clamp technique showed a positive correlation
of 25-hydroxyvitamin D (25OHD) level with insulin sensitivity
[12]. Extrapolation of the data suggested that increasing the serum
concentrations of 25OHD from 25-80 nmol/L would increase
insulin sensitivity by 60% [12], indicating that perhaps vitamin D
supplementation offers promise as an adjunctive therapy for those with
DM [13]. Mitri et al. [14] reported improved pancreatic β cell function
as well as a trend toward attenuation of the rise in HbA1c levels in
adults at high risk of T2DM who received 2000 IU of vitamin D daily
for 16 weeks. A study in children and adolescents showed that low levels
of 25OHD are associated with increasing insulin resistance in patients
at risk for diabetes [15]. Another study reported that an increase in
vitamin D levels decreased systemic inflammatory markers in patients
with T2DM [16]. However, a recent report by the Institute of Medicine
did not provide support for these extra-skeletal actions of vitamin D
[17]. Equally, a recent study failed to show any strong associations of
25OHD with either myocardial structure or function [18]. |
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| There is a high prevalence of vitamin D deficiency in patients with
TIDM and T2DM [19,20]. This vitamin D deficiency is often attributed
to sequestration in fat depots, lack of sun exposure, and insufficient
intake of vitamin D containing foods. However, the effect of hepatic
dysfunction on the critical step of hydroxylation of pre-vitamin D at
the 25 position has not been adequately described in those with DM. |
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| Therefore, to achieve the goal of glycemic control in diabetes,
euglycemia, it will be necessary to investigate beyond the conventional
modalities of diabetes management. It will be necessary to conduct
studies examining the roles of hepatic dysfunction and associated
vitamin D deficiency on glycemic control in patients with diabetes
mellitus. My colleagues and I have embarked on this mission. |
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| References |
| |
- Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol (1995) 75: 894-903.
- de Boer IH, Sibley SD, Kestenbaum B, Sampson JN, Young B, et al. (2007) Central obesity, incident microalbuminuria, and change in creatinine clearance in the epidemiology of diabetes interventions and complications study. J Am Soc Nephrol 18: 235-243.
- [No authors listed] (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet 352: 837-853.
- Petitti DB, Klingensmith GJ, Bell RA, Andrews JS, Dabelea D, et al. (2009) Glycemic control in youth with diabetes: The SEARCH for diabetes in Youth Study. J Pediatr 155: 668-672.
- Heinemann L(2010) New ways of insulin delivery. Int J Clin Pract 29-40.
- Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, et al. (2006) Prevalence of fatty liver in children and adolescents. Pediatrics 118: 1388-1393.
- Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, et al. (2003) Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 143: 500-505.
- Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, et al. (2006) Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 91: 4287-4294.
- Liangpunsakul S, Chalasani N (2011) Serum vitamin D concentrations and unexplained elevation in ALT among US adults. Dig Dis Sci 56: 2124-2129.
- Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, et al. (2002) High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51: 1889-1895.
- Nadeau KJ, Klingensmith G, Zeitler P (2005) Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase. J Pediatr Gastroenterol Nutr 41: 94-98.
- Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79: 820-825.
- Inzucchi SE, Maggs DG, Spollett GR, Page SL, Rife FS, et al. (1998) Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338: 867-872.
- Mitri J, Dawson-Hughes B, Hu FB, Pittas AG (2011) Effects of vitamin D and calcium supplementation on pancreatic ß 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. Am J Clin Nutr 94: 486-494.
- Kelly A, Brooks LJ, Dougherty S, Carlow DC, Zemel BS (2011) A cross-sectional study of vitamin D and insulin resistance in children. Arch Dis Child 96: 447-452.
- Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Kalayi A, et al. (2012) Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab Res Rev.
- Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, et al. (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the institute of medicine: what clinicians need to know. J Clin Endocrinol Metab 96: 53-58.
- van Ballegooijen AJ, Snijder MB, Visser M, Kamp O, Dekker JM, et al. (2012) Vitamin D in Relation to Myocardial Structure and Function after Eight Years of Follow-Up: The Hoorn Study. Ann Nutr Metab 60: 69-77.
- Di Cesar DJ, Ploutz-Snyder R, Weinstock RS, Moses AM (2006) Vitamin D deficiency is more common in type 2 than in type 1 diabetes. Diabetes Care 29: 174.
- Ozfirat Z, Chowdhury TA(2010) Vitamin D deficiency and type 2 diabetes. Postgrad Med J 86: 18-25.
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