Malnutrition-related Diabetes Mellitus Research Articles

Fibrocalculous pancreatic diabetes

Chronic Pancreatitis and the type of diabetes associated with it have been named as “Fibrocalcific Pancreatic Diabetes” (FCPD). Initially categorized by WHO in 1985 as a subtype of Malnutrition Related Diabetes Mellitus (MRDM), FCPD has subsequently been included as a disease of the exocrine pancreas under other specific forms of diabetes. Despite many years since its first description, the etiopathogenesis of FCPD remains obscure. While insulin secretion defects are definitely the crux of the problem, there is growing body of evidence to suggest that insulin resistance may play a key role in glucose metabolism in these individuals. Moreover, the role of free fatty acids, counter-regulatory hormones like glucagon and impact of hepatic and peripheral lipid distribution on the dynamics of insulin secretion remains to be explored. Other factors related to alterations in energy expenditure may compound the pathogenetic picture. In fact, not all people with Fibro calculous Pancreatitis will develop diabetes and a search for the exact triggers for hyperglycemia might provide the clue to this enigmatic disease pathophysiology.

An Atypical Form of Diabetes Among Individuals With Low BMI.

Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes. State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy. The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D. These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.

An Atypical Form of Diabetes Among Low Body Mass Index Individuals in India

Background: Diabetes among low BMI individuals has been recognized for over 60 years as an entity that is prevalent in low- and middle-income countries (LMICs), and formally classified as Malnutrition-Related Diabetes Mellitus by the World Health Organization (WHO) in 1985. However, the WHO withdrew this category in 1999, citing a lack of supportive evidence. Definitive metabolic characterization of these individuals is therefore essential to establish that this is a distinct form of diabetes. Methods: State-of-the-art, dynamic metabolic studies were used to characterize a group of underweight (BMI 18.3±0.2 kg/m2) Southern Indian individuals with diabetes (“Low BMI Diabetes”; LD) in whom all currently known forms of diabetes were excluded by careful immunogenetic analysis. They were compared with four demographically-matched groups: type 1 diabetes (T1D), type 2 diabetes (T2D), and two groups of non-diabetic subjects who were BMI-matched to LD and T2D. To overcome ‘glucose toxicity‘, all subjects with diabetes underwent correction of hyperglycemia. Insulin secretion was assessed by C-peptide deconvolution, following a mixed-meal tolerance test. Hepatic and peripheral insulin sensitivity were analyzed using tracer-based stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Body composition was measured by Dual Energy Absorptiometry (DEXA) and hepatic and myocellular lipid contents were assessed by 1 H-nuclear-magnetic-resonance-spectroscopy. Findings: Metabolic profiles of LD subjects were distinct from T1D and T2D. Insulin secretion was substantially lower in LD than in T2D, yet higher than in T1D. Although insulin sensitivity varied among LD subjects, they were more insulin sensitive than T2D subjects. Their peripheral insulin sensitivity did not differ from T1D subjects. Endogenous glucose production, a marker of hepatic insulin resistance, was similar in LD compared to T1D subjects, yet lower than in T2D. LD subjects also showed heterogeneity of visceral adipose tissue (VAT) and hepatocellular fat, with VAT averaging higher than T1D subjects, while both were significantly lower than T2D subjects. Additionally, compared to lean-nondiabetic subjects, LD subjects had lower insulin secretion, similar peripheral and hepatic insulin sensitivity, and higher VAT and hepatocellular fat. Interpretation: These studies are the first to demonstrate that low BMI individuals with diabetes in LMICs have a unique metabolic profile. Following correction of glucose toxicity, these individuals are characterized by markedly impaired insulin secretion, variable peripheral insulin sensitivity, and heterogeneity in visceral and hepatocellular triglyceride levels. These findings demonstrate that diabetes among low BMI individuals in LMICs is a distinct entity that warrants further investigation. Funding Information: This study was supported by the Global Diabetes Institute of the Albert Einstein College of Medicine. Declaration of Interests: None declared. Ethics Approval Statement: These comprehensive metabolic studies were performed at the Department of Endocrinology, Christian Medical College (CMC) Vellore, India, in collaboration with the Global Diabetes Institute, Albert Einstein College of Medicine, New York, USA. Approval was obtained from the Institutional Review Boards of both institutions. The objectives of the study were explained to all participants and informed consent was obtained. The study protocol was conducted in accordance to the declaration of Helsinki.

1743-P: Metabolic Characteristics of Diabetes among Low-BMI Individuals in India

Diabetes among low BMI individuals has been recognized globally for over 60 years, and classified by WHO as malnutrition-related diabetes mellitus in 1985. Despite its prevalence in low and middle income countries, this condition has never been comprehensively studied. State of the art metabolic studies were performed in 20 South Indian men with Low BMI Diabetes (LD; BMI 18.3 ± 0.9 kg/m2), after excluding monogenic and immune diabetes, and visible pancreatic pathology. Other groups were studied: T1D, T2D, and nondiabetic subjects (BMI-matched to LD and T2D). Insulin secretion was assessed by C-peptide deconvolution following a mixed-meal tolerance test. Peripheral and hepatic insulin sensitivity were analyzed using tracer-based (6,6-deuterated glucose), stepped hyperinsulinemic-euglycemic pancreatic clamps following correction of glucose toxicity. LD subjects were distinct from both T1D and T2D. Insulin secretion was significantly lower in LD than in T2D subjects, yet higher than in T1D. LD subjects were more insulin sensitive than T2D; glucose uptake and endogenous glucose production did not differ from lean nondiabetic or T1D subjects. These comprehensive studies are the first to demonstrate that LD individuals are characterized by markedly impaired insulin secretion yet preserved insulin sensitivity. Thus, diabetes in low BMI individuals is a distinct entity that warrants further investigation. Disclosure E. Lontchi Yimagou: None. R. Das Gupta: None. S. Anoop: None. S. Kehlenbrink: None. J. Moy: None. A. Manavalan: None. P.M. Mathias: None. A. Goyal: None. M. Carey: None. D.T. Stein: None. N. Thomas: None. M. Hawkins: None. Funding National Institutes of Health (R01DK069861)

Malnutrition Related Diabetes Mellitus in Indian Population

Malnutrition related diabetes mellitus (MRDM) is rare type of diabetes associated with long term malnutrition and is not uncommon in India. Diabetes mellitus is the most common endocrine disorder of multifactorial aetiology and has been linked to both chronic under nutrition and obesity. Malnutrition is often related to deficient micro and macro nutrients, unhealthy behaviours and low socioeconomic status. Various clinical studies have underlined the relationship between malnutrition and diabetes mellitus. In the present review, we mainly explored malnutrition related diabetes mellitus in Indian population. Maternal under nutrition during pregnancy causes a decrease in the fetal intrauterine development rate known as intrauterine growth retardation (IUGR). Malnutrition majorly causes persistent insulin deficiency, glucose intolerance and insulin resistance and there by increases the risk of diabetes in Indian population. In this study we have also discussed the pathogenesis of MRDM and their management like self- dietary management and evidence based individualized nutritional therapy.

Atypical forms of diabetes mellitus in Africans and other non-European ethnic populations in low- and middle-income countries: a systematic literature review.

BackgroundAtypical presentations of diabetes mellitus (DM) have been reported in non-European ethnic populations under various names. It is unclear whether those names are used for the same or different clinical phenotypes. Unclear terminology may lead to inappropriate treatment and an underestimation of the burden caused by atypical diabetes phenotypes overlapping with classic types of diabetes. This review aimed to describe the terms used for atypical forms of diabetes and to investigate whether the terms are used for similar or different phenotypes.MethodsPubMed and Scopus were searched for relevant publications in French or English available before 15 September 2015 using the terms: ”Atypical diabetes”, “Malnutrition Related Diabetes Mellitus (MRDM)”, “Fibro-calculus pancreatic diabetes (FCPD)”, Protein deficient Pancreatic Diabetes (PDPD)”, “African diabetes”, “Ketosis prone-type 2 diabetes”, “tropical diabetes”, “Flatbush diabetes”, “J-type diabetes”. Titles, abstracts screening and quality assessment were performed by two independent authors. Observational studies addressing atypical diabetes in humans aged 14 years and above were included. One author extracted data from selected articles.Results22 articles among 350 identified articles were retained for data extraction. Two atypical diabetes phenotypes were identified, each of them with a variety of names but similar definitions. One phenotype occurred in very thin people less than 30 years of age, typically from poor socio-economic backgrounds and requires insulin for life. It differs from type 1 diabetes in the tolerance of high blood glucose without ketosis in the absence of exogenous insulin. The second phenotype resembles type1 diabetes as it presents with ketosis at onset but responds well, as type2 diabetes, to oral hypoglycemic drugs after initial stabilization with insulin. It occurs in individuals who are usually over 30 years of age, with normal or overweight and absence of auto antibodies mainly found in type 1 diabetes.ConclusionThe scarce existing literature used various terms for similar diabetes phenotypes. Agreement on nomenclature for the various forms of diabetes using the above reported characteristics are needed in populations where atypical forms of diabetes exist as well as better characterization of phenotypes and genotypes to inform evidence based treatment.

Conceptual study of malnutrition related diabetes mellitus

The Diabetes mellitus (DM) is a metabolic disease characterized by absolute or relative insulin deficiency. Type 1 diabetes is commonly known as juvenile diabetes, because it typically strikes during childhood and sometimes adolescents, and young age group. Now in the whole world nearly about 24% of population is suffering from diseases. The first widely accepted classification of diabetes mellitus was published by WHO in 1980 named them as IDDM (type-1) and NIDDM (type-2) and Malnutrition related diabetes mellitus (MRDM) was introduced in 1985. In India Malnutrition has high prevalence rate Malnutrition during intrauterine and early childhood period may impair growth and development. This review provides an overview of Juvenile Diabetes in children with MRDM. The juvenile diabetes and MRDM is a palliative disease. It cannot be completely cured, but can be controlled by medication, food, Ayurvedic Chikitsa and Lifestyle Changes.

Fibrocalculus Pancreatic Diabetes in a Young Female: A Rare Form of Secondary Diabetes

Fibrocalculus pancreatic diabetes (FCPD) is a rare form of diabetes. FCPD is one of the two forms of malnutrition related diabetes mellitus (MRDM), the other one being protein deficient diabetes mellitus (PDDM). Fibrocalculus pancreatic diabetes was introduced for this form of diabetes by the World Health Organization study group report on diabetes. Several case reports of FCPD have been described in literature from tropical, poverty striken African and Asian countries for over 50 years. In India most cases are reported from Southern and Eastern India specifically from Kerala, Chennai and Odisha. From Jharkhand it is not reported.

A sub-Saharan African perspective of diabetes

Diabetes mellitus is an important and increasing cause of morbidity and mortality in sub-Saharan Africa. Accurate epidemiological studies are often logistically and financially difficult, but processes of rural-urban migration and epidemiological transition are certainly increasing the prevalence of type 2 diabetes. Type 1 disease is relatively rare, although this may be related to high mortality. This diabetic subgroup appears to present at a later age (by about a decade) than in Western countries. Variant forms of diabetes are also described in the continent; notably 'atypical, ketosis-prone' diabetes, and malnutrition-related diabetes mellitus. These types sometimes make the distinction between type 1 and type 2 diabetes difficult. Interestingly, this is also a current experience in the developed world. As more detailed and reliable complication studies emerge, it is increasingly apparent that African diabetes is associated with a high complication burden, which is both difficult to treat and prevent. More optimistically, a number of intervention studies and twinning projects are showing real benefits in varying locations. Future improvements depend on practical and sustainable support, coupled with local acceptance of diabetes as a major threat to the future health and quality of life of sub-Saharan Africans.

No association of SUMO4 M55V with autoimmune diabetes in Asian‐Indian patients

Autoimmune diabetes [type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and part of malnutrition-related diabetes] has been shown to have genetic predisposition. Studies in IDDM 5 have lead to the discovery of a novel polymorphism 163 A-->G, of SUMO4 (small ubiquitin-related modifier) gene, associated with risk to T1DM in Asians, but not in Caucasians. We studied patients with T1DM (n = 134), patients with LADA (n = 101), patients with malnutrition-modulated diabetes mellitus (n = 66) and patients with fibrocalculous pancreatic diabetes (n = 43) and healthy controls subjects (n = 114) from Cuttack, India. Polymerase chain reaction-sequence-specific primer (PCR-SSP) was used to amplify the 163 A-->G sequences. Restriction fragment length polymorphism (RFLP) was performed using restriction enzyme Taq I (PCR-RFLP). Differences in the allelic frequencies of the A and the G alleles were tested statistically using Fisher's exact test or chi-squared test wherever appropriate. P-values were considered significant when equal to or less than 0.05. No significant association was detected between SUMO4 M55V and T1DM susceptibility in Asian-Indians. Comparison of the A and G alleles with HLA DR3-DR4 did not result in any significant P-values. No significant association was found between SUMO4 M55V and LADA or malnutrition-related diabetes mellitus (MRDM). Our results show that Asian-Indians with T1DM are different from other Asian populations. Asian-Indians show more similarity to Caucasians with respect to the association of SUMO4 M55V variant in T1DM. Association studies on Asian-Indian patients with LADA and MRDM showed no significant difference in the presence of the A and the G alleles when compared to healthy controls.

Effect of Wainan Rogo on body weight and plasma glucose in Wistar rats.

Wainan Rogo (WR) is a deep-fat fried dough made from grated fresh cassava. It was found in a cross sectional case-control study to have a risk factor 3.2 times higher in diabetic than non diabetic indigenes of Borno State of Nigeria. This study examines the chemical composition, and effects of WR on body weight and blood glucose in Wistar rats. The study found a higher fat and lower protein composition of the WR diet, and found a higher plasma glucose in the WR fed rats and a more significant weight loss in this group than in the control (CF) fed rats. The findings of this study seem to support the high risk for diabetes associated with WR in the cross sectional study. The chemical composition of WR and its effect on body weight and blood glucose are further discussed, with a call for further studies of the food as a marker in the search for the pathophysiology of Malnutrition-Related Diabetes Mellitus (MRDM).

Association of HLA class II alleles with different subgroups of diabetes mellitus in Eastern India identify different associations with IDDM and malnutrition-related diabetes.

Genetic studies of Malnutrition related diabetes are few. We have analyzed HLA class II gene polymorphism in different types of diabetes mellitus patients from Cuttack in Eastern India. Patients with insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and malnutrition-related diabetes mellitus (MRDM), which is subdivided into protein-deficient diabetes mellitus (PDDM) and fibrocalculous pancreatic diabetes (FCPD), were studied and their associations with autoantibody markers. IDDM and PDDM were associated with DR3 and DQ2 but not DR4 and DQ8. FCPD was positively associated with DQ9 (A*0201-B*0303). The association of DQ9 with FCPD suggests differences in the genetic background for susceptibility between IDDM and MRDM in the Cuttack population. There is no association seen between HLA-DR-DQ and NIDDM patients from Eastern India. Clinical classification of diabetes into IDDM, NIDDM and MRDM does not identify the underlying pathological mechanisms. Presence of autoantibodies to IDDM autoantigens in clinical MRDM and NIDDM identifies the slow-onset form of IDDM. Due to the absence of autoantibody assays for diagnosis of IDDM in India, slow onset IDDM is not diagnosed and the patients are classified as NIDDM or MRDM. Our study demonstrates that the presence of GAD65 antibody and DR3-DQ2 positivity in MRDM and NIDDM patients in Eastern India would suggest the presence of slow-onset IDDM. Our data would indicate alternatively that MRDM can coexist with IDDM in these patients and malnutrition could be one of the reasons for the slower onset in IDDM-prone individuals.

Is protein‐deficient diabetes mellitus a pancreatitis?

Malnutrition-related diabetes mellitus is a distinct clinical entity subdivided into protein-deficient diabetes mellitus (PDDM) and fibrocalculus pancreatic diabetes (FCPD). Whereas FCPD has obvious pancreatitis manifested by pancreatic duct calculi, the evidence for involvement of the pancreas in PDDM is limited to the presence of ketosis-resistant hyperglycaemia. We studied 10 patients with PDDM biochemically and radiologically. Endoscopic retrograde cholangiopancreatography was performed to determine if they had any evidence of chronic pancreatitis. Their mean faecal chymotrypsin level was low (13.2+/-5.72 microg/g), as was their basal c-peptide value (0.35+/-0.15 mmol/L). Islet cell antibodies were not detected in any of these patients. Ultrasound examination revealed pancreatic atrophy. In two patients, however, the pancreas was bulky. The ERCP showed generalized thinning of the pancreatic duct, measuring 2.4+/-0.06mm in the head, 2.01+/-0.08 mm in the body and 1.02 +/- 0.03 mm in tail region; side branches were seen but they were too sparse and thin. The significance of these changes is not clear, but they may represent an ongoing pancreatic disease and may, indeed, be the earliest changes of chronic pancreatitis.

Relation between malnutrition and development of diabetes mellitus.

Obesity and increased dietary intake of high fat are considered important factors involved in the development of type 2 diabetes, as they correlate to the prevalence of diabetes in different populations and are both associated with insulin resistance, which is an important pathogenic event for diabetes (1,2). However, epidemiological studies have shown that diabetes is common also in populations where obesity is not a major concern for health (3). In fact, in some developing countries, the prevalence of diabetes exceeds that of more developed countries, as, for example, has been shown in studies in Bangladesh (4) and India (5). The question of whether also malnutrition is detrimental for glucose metabolism and may contribute to the development of diabetes has therefore been raised. This would also be supported by clinical studies showing distinct and specific clinical characteristics of diabetes in malnourished subjects when compared to nonmalnourished subjects, such as early age of onset, requirement of insulin to control hyperglycemia in conjunction with ketosis resistance in the absence of insulin therapy, and the presence of pancreatic calculi, in addition to the clinical manifestations of malnutrition (6–9). Based on these epidemiological and clinical observations, WHO recognized, in 1985, malnutrition-related diabetes mellitus (MRDM) as a special subtype of diabetes, different from type 1 (IDDM) and type 2 diabetes (NIDDM) (6). However, using malnutrition in the classification of diabetes has been questioned, because malnutrition has also been considered to be a mere coincidence with diabetes, which exaggerates or modulates the clinical feature of the disease (10,11). In fact, several arguments have been put forward against the use of MRDM as a distinct entity of diabetes. One argument is that it has not been convincingly demonstrated that malnutrition results in permanent diabetes and another argument is that the classification of diabetes into type 1 or type 2 relies on clinical aspects, not pathogenesis (6,10). In addition, malnutrition by itself is a vague condition that is difficult to define, as it is usually assessed by combined interpretation of data from the dietary history, anthropometric data, clinical examination, and laboratory investigations without strict criteria. Malnutrition is also inhomogeneous, because it includes both single and combined nutrient deficiencies as well as global energy deficiency. Moreover, the clinical characteristics thought to be specific for MRDM may also be identified in diabetic subjects without a history of malnutrition (10,12). Therefore, the new classification system of the American Diabetes Association does not consider MRDM a distinct entity of diabetes (11). Instead, fibrocalculus pancreatic diabetes (FCPD), being a former subgroup of MRDM, has been classified as an exocrine pancreatic disease, and protein-deficient diabetes mellitus (PDDM) is considered a condition modulating the clinical features of existing diabetes. Nevertheless, apart from the issue of classification, the role of malnutrition on glucose homeostasis remains elusive and needs further studies to designate it as a modulating factor in diabetes. As previously reviewed by Rao (7), malnutrition may cause diabetes as a priInternational Journal of Pancreatology, vol. 26, no. 3, 125–130, December 1999 © Copyright 1999 by Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4197/99/26:125–130/$11.50

Serum and urinary magnesium in young diabetic subjects in Bangladesh

Magnesium imbalance, implicated in diabetes mellitus both as a cause and a consequence, has not yet been investigated in subgroups of subjects with malnutrition-related diabetes mellitus. which is prevalent in young patients in tropical developing countries such as Bangladesh. The present study evaluated the serum and urinary magnesium concentrations in groups of young diabetic subjects in Bangladesh. Forty patients newly diagnosed with diabetes [13 with fibrocalculus pancreatic diabetes (FCPD), 13 with protein-deficient diabetes (PDDM), and 14 with type 2 diabetes mellitus] were studied along with 13 healthy control and 13 malnourished control subjects [body mass index (in kg/m2) < 19]. Magnesium was measured by atomic absorption spectrophotometry. Malnutrition itself was not related to the serum glucose (fasting: 3.68+/-0.74 and 4.11+/-0.29 mmol/L; postprandial: 6.30+/-0.41 and 6.00+/-0.24 mmol/L for healthy and malnourished control subjects, respectively) or serum or urinary magnesium (serum: 0.73+/-0.03 and 0.75+/-0.05 mmol/L: urinary: 232+/-124 and 243+/-88 mmol Mg/mol creatinine for healthy and malnourished control subjects, respectively) concentration. Subjects with FCPD and PDDM had significantly lower serum magnesium concentrations (PDDM: 0.68+/-0.06 mmol/L, FCPD: 0.66+/-0.07 mmol/L) than those in both control groups. In contrast with 0% of healthy and 7.7% of malnourished control subjects, 42.85% of type 2 diabetic subjects, 61.54% of those with PDDM, and 69.23% of those with FCPD were hypomagnesemic. Subjects with FCPD and PDDM had significantly higher urinary excretion of magnesium than the healthy and malnourished control subjects and the type 2 diabetic subjects. Hypermagnesuria paralleled hypomagnesemia. Malnutrition may not itself give rise to glucose intolerance, and serum magnesium deficiency seems to be a consequence rather than a cause of diabetes mellitus.

Antioxidant status, oxidative stress and DNA damage in the aetiology of Malnutrition Related Diabetes Mellitus

Undernutrition is a preeminent feature of the two major clinical syndromes, protein dependent diabetes mellitus (PDDM) and fibrocalculous pancreatic diabetes (FCPD) that has been grouped together under the term malnutrition related diabetes mellitus (MRDM).[l] Although, MRDM represents only a few percent of the world population suffering from diabetes, it is a major health problem within developing countries. Investigation of these forms of the disease indicates that a genetic predisposition cannot be clearly established, and several hypotheses related to dietary-deficiency and environmental chemical exposure have been proposed. Oxidative stress induced by oxygen free radicals has been implicated in the pathogenesis of many human diseases in recent years.[2] It is becoming increasingly plausible that antioxidant deficiency leading to the exposure of pancreatic B-cells to increased oxidative stress may be implicated in the aetiology and pathogenesis of MRDM. increased oxidative stress (a high prooxidant/antioxidant ratio) which is based on evidence of increased lipid peroxidation and reduced antioxidant reserve.[3] A deficiency in the nutritional supply and availibility of antioxidants which may occur in MRDM may have consequences in terms of failure of the first line of defence against oxygen radical induced damage.[4] The aim of the study was to assess the antioxidant status and levels of oxidative stress and DNA damage in malnourished patients displaying PDDM (n=24), FCPD (n=14), non-insulin dependent diabetes mellitus (NIDDM) (n=46), and age matched controls (n=67). All diabetic patients were under 30 years and newly diagnosed to avoid complicating variables such as insulin therapy and control subjects were matched for age, BMI and socioeconomic status. Plasma vitamins A, C, and E were measured by HPLC [5,6], whilst antioxidant enzymes in red cell concentrate were measured on the Cobas Fara autoanalyser[7-10]. DNA damage within nucleated blood cells was measured using a sensitive ELISA.[11]

Islet-cell antibodies in malnutrition-related diabetes mellitus from North India

The etiology of malnutrition-related diabetes mellitus (MRDM) — protein-deficient pancreatic diabetes (PDPD) and fibro-calculous pancreatic diabetes (FCPD) — is unclear. We studied the role of autoimmunity against pancreatic islet cells in the etiology of these two subtypes of MRDM by measuring islet-cell antibodies (ICA) in 23 patients with PDPD, 25 with FCPD and 62 with Type 1 diabetes. Three patients (13%) with PDPD had detectable ICA, including a patient with a high titre of ICA (> 80 JDF units). The frequency of ICA in patients with PDPD was significantly lower than subjects with Type 1 diabetes ( 22 62 , 35%; P < 0.05). Among patients studied at onset, ICA prevalence was lower in the PDPD patients ( 1 7 , 14%) compared to subjects with Type 1 diabetes ( 8 20 , 40%). No patient of FCPD had detectable ICA ( P < 0.001 vs. Type 1 diabetes subjects). We conclude that autoimmunity may play a role in the etiology of some patients with the PDPD subtype of MRDM. However, FCPD is unlikely to have an autoimmune etiology.

Insulin resistance during euglycemic clamp studies in chronically undernourished rats with mild streptozocin diabetes

Malnutrition has been shown to impair insulin sensitivity, but it is not known whether this effect has any impact on coexisting diabetes. Insulin sensitivity was therefore studied using the glucose clamp technique in rats with chronic nutritional deprivation superimposed on mild streptozocin (STZ) diabetes mellitus. In pair-feeding experiments, 4-week-old littermate rats were either allowed ad libitum access to food or restricted to 50% of ad libitum intake for 8 weeks, and were injected with STZ 40 mg/kg intraperitoneally halfway through the experiment. Fasting plasma glucose (FPG) was similar in both groups of rats, but fasting plasma insulin (FPI) was lower in the undernourished group ( P = .016). Undernourished rats were significantly more insulin resistant during euglycemic hyperinsulinemia of the same degree, with glucose disposal rate being impaired by 50% as compared with that in ad libitum—fed diabetic littermates (24.4 ± 2.8 v 51.5 ± 4.4 μmol/kg/min, P = .0008). The insulin sensitivity index was significantly lower in the undernourished group (3.03 ± 0.32 v 5.67 ± 0.6, P = .0057). The results show that chronic undernutrition markedly reduces insulin sensitivity in rats with mild STZ diabetes. This is further evidence that chronic undernutrition is a deleterious modifying influence on coexisting diabetes mellitus. It suggests that the insulin resistance of malnutrition-related diabetes mellitus (MRDM) could potentially be an acquired defect mediated by the coexistent undernutrition, rather than a “distinctive” feature that is intrinsically unique to this diabetic syndrome.

A study of thyroid function and prevalence of thyroid autoantibodies in an African diabetic population

It is generally believed that autoimmune disorders are uncommon in Africans. Some workers have argued that insulin-dependent diabetes mellitus (IDDM) is rare in Africa on account of this reduced proneness to autoimmunity. However, it is undetermined whether or not Africans with IDDM have increased prevalence of thyroid dysfunction and autoimmunity, two phenomena strongly associated with Caucasian IDDM. We determined thyroid function and the prevalence of thyroid autoimmunity in IDDM Africans. The results are compared with those of a nondiabetic group and a group with non-insulin-dependent diabetes mellitus (NIDDM). Thyroid hormone levels were significantly lower in IDDM patients than in the control population and the NIDDM population. Subclinical hypothyroidism was present in 21% of the 28 IDDM patients. One patient was hypothyroid and another hyperthyroid. Of the 60 NIDDM patients, 5 (8.3%) had subclinical hypothyroidism. Forty-six percent of the IDDM patients had significant levels of serum thyroid autoantibodies (TAAB). This was significantly higher than the 1.4% and 1.7%, respectively, in the controls and NIDDMs. Presence of TAAB in the patients was strongly associated with thyroid dysfunction, female preponderance, and duration of diabetes mellitus. Thyroid dysfunction and autoimmunity are common in Nigerians clinically diagnosed as IDDM, and have prevalence rates comparable to other populations but higher than rates previously reported from some other African groups. The increased prevalence of thyroid autoimmunity in the IDDM supports the view that these patients are true IDDMs rather than variants of NIDDM or malnutrition-related diabetes mellitus (MRDM) as has been suggested by some workers.

Fibrocalculous Pancreatic Diabetes in Pune, India: Clinical features and follow-up for 7 yr

To study clinical features of fibrocalculous pancreatic diabetes from this clinic, to compare these with the published criteria of malnutrition-related diabetes mellitus, and to conduct serial follow-up of these patients to study difficulties in their treatment. Details of presenting symptoms, anthropometry, diabetic tissue damage, treatment, and follow-up of 55 patients with fibrocalculous pancreatic diabetes (pancreatic calculi demonstrated on X-ray and sonography) treated during the last 7 yr were studied. Many patients did not fit the accepted criteria of malnutrition-related diabetes. Thus, 17 (31%) were diagnosed after 30 yr of age and 23 (42%) had a body mass index > 18 kg/m2, and the daily dose of insulin in these patients (mean 0.8 U/kg) was similar to that in the IDDM patients (mean 1.0 U/kg). The two pathognomonic complaints (pancreatic pain and steatorrhea) were not always present. Many patients took very irregular treatment, but none suffered diabetic ketoacidosis despite stopping insulin for long periods of time; 33% of patients had some diabetic tissue damage when first seen. Fourteen patients were lost to follow-up, and 11 died during the follow-up. Clinical features of these fibrocalculous pancreatic diabetes patients were somewhat different than the classic descriptions. A need exists to reconsider classification of FCPD under malnutrition-related diabetes mellitus. Many patients receive irregular treatment, and a substantial proportion die within a few years of diagnosis, many as a result of preventable causes.