Clinical and aetiological profile of early onset diabetes mellitus: data from a tertiary care centre in the Indian subcontinent.AH Zargar, MH Bhat, BA Laway, SR Masoodi
Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. , India
BACKGROUND: Type 2 diabetes mellitus (DM) in youth is emerging as a serious clinical entity and its incidence has increased over the years. AIM: To analyse the causes of DM in the age group of <40 years of age. SETTINGS AND DESIGN: Tertiary care centre; retrospective analysis of data from January 1990 to December 1999. SUBJECTS AND MATERIAL: Analysis of data of all the subjects of DM in whom disease started before the 40th birthday. RESULTS: 724 subjects were detected to have diabetes mellitus before their 40th birthday. Of these, 205 had Type 1, 174 had Type 2 and 48 had fibrocalculous pancreatic diabetes. Males outnumbered in Type 1 and fibrocalculous pancreatic diabetes while as females in Type 2 diabetes mellitus. Chronic complications were more common in Type 2 diabetes mellitus. CONCLUSION: Type 2 diabetes mellitus is becoming an important cause of diabetes in subjects with onset of disease at younger age.
Keywords: Adolescent, Adult, Age Distribution, Age Factors, Age of Onset, Child, Diabetes Mellitus, Insulin-Dependent, complications,diagnosis,epidemiology,etiology,Diabetes Mellitus, Non-Insulin-Dependent, complications,diagnosis,epidemiology,etiology,Female, Human, Incidence, India, epidemiology,Male, Obesity, complications,Prevalence, Sex Distribution, Sex Factors,
Till recently, diabetes mellitus (DM) was mainly characterised into two types. Type 1, a distinct entity, affecting <40 years and Type 2, a heterogeneous group, characterized by a combination of insulin resistance and/or insulin deficiency affecting individuals of >40 years of age. In past, Type 1 DM was considered to be rare in adults but same is not considered true at present. However, Type 2 DM still continues to be the commonest type of DM in this age group and its prevalence is increasing. A surprising observation in recent years has been the documentation of Type 2 DM in children. There is a unanimous agreement that Type 2 DM in youth is emerging as a serious clinical entity and its incidence has increased between 1982 to 1994. Fibrocalculous pancreatopathy - a secondary form of DM, mostly seen in tropical countries with few exceptions is also an important cause of DM in the age group of <40 years.
In the present study, we analysed the causes of diabetes mellitus in the age group of <40 years of age.
The present study consists of analysis of data of all the subjects of DM in whom disease started before the 40th birthday. From January 1990 to December 1999, 427 subjects were recognised whose records were complete. These were screened for age, sex and duration of symptoms related to DM or its complications, actual duration of DM, family history of DM, episodes of ketoacidosis. Weight, height, body mass index, blood pressure on admission, presence of neuropathy, nephropathy, retinopathy were noted. Neuropathy was defined as failure to elicit the knee and/or ankle reflexes after reinforcement with or without symptoms of neuropathy or gross sensory disturbance in both feet, in the absence of any other cause of neuropathy. Nephropathy was defined as quantitative 24-hour urine protein excretion of >500mg per 24 hours, in the absence of other renal diseases. Retinopathy was established by an ophthalmologist/endocrinologist and classified as background or proliferative retinopathy according to Kohner et al classification. Investigations studied were electrocardiogram, X-ray chest/abdomen, 24-hour urinary protein, creatinine, serum urea, creatinine, lipid profile and fructosamine (in some cases). Subjects were clinically classified into three main types of diabetes mellitus
1. Type 1 DM: Subjects with an episode of ketoacidosis and requiring insulin for survival or patients who required insulin within first year of diagnosis for control of hyperglycaemia.
2. Type 2 DM: Subjects without an episode of ketoacidosis, controlled on oral hypoglycemic agents for more than a year after diagnosis
3. Fibrocalculous pancreatic diabetes (FCPD): Diabetes mellitus with or without pain abdomen with pancreatic calcification on plain X-ray abdomen.
Over a period of a decade, 427 subjects of diabetes mellitus were evaluated who started the disease before their 40th birthday. Being a retrospective study, diagnosis of DM was based on previous WHO criteria. Out of 427 patients, 205 subjects qualified for the diagnosis of Type 1 DM, 174 qualified for the diagnosis of Type 2 DM and 48 had FCPD making Type 1 DM as the commonest form of DM before the 40th birthday. Fig. 1 gives the age distribution of three types of DM. As is evident from the figure, Type 1 DM starts peaking in the age group of 2nd and 3rd decade whereas FCPD and Type 2 DM peak around 3rd and 4th decade. The sex distribution in three types of DM was not uniform. Males outnumbered females in both Type 1 (123 vs.82) and FCPD (29 vs.19) whereas females did so in Type 2 DM (230 vs.130). Family history was positive in 3.4%, 4.2% and 4.6% in type 1, FCPD and type 2 respectively. Over-all mean body mass index (BMI) was 16.7 ? 4.70Kg/m2. Only 18% of subjects with Type 2 DM had BMI of >25Kg/m2 whereas none of the patients with Type 1 or FCPD had BMI of >25Kg/m2.
[Table - 1] gives the details of chronic complications in three types of DM. Nephropathy, neuropathy and retinopathy were more common in Type 2 DM, followed by decreasing order of occurrence in Type 1 and FCPD. [Table - 2] gives the duration of DM when these subjects were evaluated in Endocrinology Clinic. Half of the patients with Type 1 DM had duration of disease of <1year. A reverse sequence was seen in subjects with Type 2 DM. Similarity of trend was seen between FCPD and Type 1 DM.
Type 2 DM is the commonest type of DM when one estimates the prevalence especially over 40 years of age. In past, Type 1 DM was considered to affect only children and subjects <40 years of age. Our study revealed Type 1 DM as the commonest form of DM seen in the age group of <40 years, accounting for 48% of the cases followed by 40.01% with Type 2 DM. Type 1 DM is still considered to be the commoner form of DM in young. The incidence of Type 2 DM in children between 1990 and 1994 in one series was found to be 31%, rest of the subjects had Type 1 DM. Similarly 19% incidence has been reported in other series. Emergence of Type 2 DM in childhood is a new challenge. At present it has assumed epidemic proportions in Japan, Canada and North America. Increasing obesity and decreasing physical activity are the possible explanations for such a change. Fibrocalculous pancreatic diabetes (presently termed as fibrocalculous pancreatopathy) affects young people, mostly in tropical areas but we have reported its presence in the subtropical regions is equally, also.,, In our study, FCPD constituted 11.04% of the cases and mostly started in the 3rd decade. Because of their relative young age, macrovascular complications occur less frequently in them. As is evident in Fig. 1, both Type 1 and FCPD were more common in males whereas Type 2 DM was more common in females. In previous observations also, we have found Type 1 DM and FCPD to be more common in males.,,
In Mexican Americans, Type 2 DM has been found more frequently in females although the reason may not be clearly related to gender if one considers the environmental factors. In one of our previous study, we have documented female predominance in Type 2 DM although only subjects more than 40 years of age were studied in that survey. We believe in addition to obesity some genetic factor may be responsible for such an observation. A strong family history of DM is seen more frequently with Type 2 rather than Type 1 DM, although exact nature of family descent is not understood except in maturity onset diabetes of young (MODY).
In our study, only 4.6% of DM had a positive family history of DM, however, possibility of more undetected asymptomatic cases cannot be ruled out. In our earlier study, we documented 5% of subjects with FCPD having a positive family history of DM.
Most of our subjects with Type 1 DM and FCPD were non-obese. This observation is in agreement with most of the previous studies., Obesity is considered a major contributing factor in Type 2 DM. In one study using a criteria of BMI>27Kg/M2, 50% of the children were found obese. 18% of our Type 2 DM subjects had a mean BMI of >25Kg/M2. In our previous study, we found a mean BMI of 22.35Kg/m2 in males and 23.88Kg/m2 in females.
In this study, chronic complications of DM were seen more often in Type 2 than Type 1 [Table - 2]. We believe this observation is related to longer duration of DM in Type 2 as compared to Type 1 (6.4 vs. 2.8 years.) and on top of that, the exact duration of DM is always underestimated in Type 2 DM because of paucity of florid symptoms. It was previously believed that chronic complications do not occur in subjects with FCPD but both acute and chronic complications have been documented time and again.,,,, Chronic diabetic complications have been demonstrated mostly to be related to glycaemic status and duration of the disease in most of the landmark studies.
[Figure - 1][Table - 1], [Table - 2]