|LETTER TO EDITOR
|Year : 2013 | Volume
| Issue : 1 | Page : 57-58
Lean type diabetes: Changing fads
Dilip Gude1, Aslam Abbas2
1 Departments of Internal Medicine; Critical Care, Princess Durru Shehvar Children's and General Hospital, Purani Haveli, Hyderabad, Andhra Pradesh, India
2 Departments of Internal Medicine, Princess Durru Shehvar Children's and General Hospital, Purani Haveli, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||17-Apr-2013|
Department of Internal Medicine and Critical Care, Hyderabad 500 001, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gude D, Abbas A. Lean type diabetes: Changing fads. Int J Health Allied Sci 2013;2:57-8
Epidemiological profile of type 2 diabetes in India is very different compared to the west. Eighty percent of type 2 diabetic patients in India are non-obese and 1/4 th of type 2 diabetics in India are of Body Mass Index (BMI) <19 kg/m 2 .  The build/habitus of these patients is often "lean" with low bodyweight, i.e., more than 20% below the ideal bodyweight for height and gender. The prevalence of lean type diabetes (LTD) with BMI <19 kg/m 2 in India ranges from 1.6% to 26%.  They display an atypical clinical, biochemical, and hormonal profile. LTDs tend to be older at diagnosis. The average age distribution in LTDs is believed to be <30 years - 20.2%, 31-40 years - 25.8%, and >40 years - 53.9%.  LTDs are distinct variants of classical Type 2 DM (neither Latent Autoimmune Diabetes of Adulthood (LADA) nor former fruste of Type 1 DM).
Leaner patients (BMI <25 kg/m 2 ) compared to obese (BMI ≥30 kg/m 2 ) may have a stronger genetic predisposition (presence of LAMA1 gene,  KCNJ15 (potassium inwardly-rectifying channel, subfamily J, member 15), etc.,) to type 2 diabetes.  KCNJ15 may be a new pharmacological target (that blocks glucose-stimulated insulin secretion) for individuals with reduced insulin secretion.
LTDs have good insulin C-peptide reserve for a prolonged period of life. LTDs may have excess extraction of insulin in hepatic bed, hyperactive cytochrome system, and non-suppressible glucokinase activity, owing to perturbed insulin kinetics and carbohydrate metabolism. These may result in hypoinsulinemia, hyperglycemia, and dyslipidemia. They have lesser insulin resistance and poorer insulin secretory capacity. Non-insulin-mediated glucose uptakes may be normal but glucose effectiveness-at-zero-insulin (GEZI) may be diminished in insulin-sensitive LTDs.  (GEZI = Glucose effectiveness at basal insulin (SG) - (insulin sensitivity index (SI) Χ basal insulin); Concept of GEZI was introduced to eliminate the effect of basal insulin on SG and estimate insulin-independent glucose uptake). 
Deterioration in the pancreatic response to glucose stimulus points to profound alteration in carbohydrate metabolism. Undernutrition and poor β-cell function (although markers of autoimmune destruction of β-cells are absent in the majority) may play etiological role in LTDs. Intramyocellular lipid (IMCL) accumulation plays an important role in causing muscle insulin resistance in LTDs, which reverses with modest weight loss.  In a study, antibodies to glutamic acid decarboxylase-65 (GAD Ab) were present in 25.3% of LTD. GAD Ab positivity correlated with younger age and lower beta cell function (homeostasis model assessment, HOMA) as compared to the GAD Ab-negative group.  Plasma FFA, IL-6, hsCRP, leptin, and triglyceride concentrations are lower in LTDs as opposed to their obese counterparts.  Angiotensin sensitivity is negatively correlated with blood glucose levels. LTDs also manifest ketosis resistance owing to impaired ketogenic process and/or deficient adipose tissue. They have moderate to severe basal hyperglycemia with much higher fasting blood glucose level than the obese. Serum insulin level is lower in LTDs than in obese type 2 diabetics, although there is no significant difference in c-peptide level (owing to excess extraction of insulin by the liver). Immunoreactive insulin levels are persistently lower in LTDs both during fasting and fed state compared to obese and normal weight DM with adequate c-peptide response to glucose. Excess extraction of insulin in the porto-hepatic circulation in LTDs leads to lower peripheral levels of insulin. LTDs show low normal values of growth hormone at basal state.
Higher prevalence of microvascular complications (peripheral neuropathy (70%), retinopathy (25%), and nephropathy (13%)) in LTDs are observed compared to diabetics with ideal body weight or obese diabetic patients.  These are related to duration of diabetes and glycemic control. Higher incidence of infection (increased rate of pulmonary tuberculosis  ) and stroke are more common features in the LTDS while coronary artery disease (CAD) and hypertension are characteristically absent. LTDs have lower cholesterol, higher HDL cholesterol (excess hepatic lipase activity), higher triglyceride, free-fatty acids, and lactate levels. In LTDs, increase in urinary albumin excretion may be an indicator for development of proliferative diabetic retinopathy.  The insulin resistance in LTDs is not related to anthropometric parameters like central obesity and waist-hip ratio.
Sulfonylureas and other oral hypoglycemic agents (OHA) benefit LTDs at earlier stages, but eventually they may succumb to secondary OHA failure (observed in about 27%).  The presence of insulin resistance and a good beta-cell reserve for insulin, despite lean habitus, enables LTDs responsive to OHA initially.
LTD is an increasingly common entity that might pose diagnostic challenge and warrants prompt awareness by clinicians of its features and management.
| Acknowledgment|| |
We thank our colleagues and staff of Internal medicine.
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