Diabetes in adolescents without obesity in India: An underrecognized phenotype

Abstract

Adolescent type 2 diabetes mellitus (T2DM) is on the rise in India and is commonly attributed to co-existence of overweight and obesity in adolescents. In this line, a study by Maheshwari et al titled ‘Prevalence of obesity, determinants, and its association with hyperglycaemia among community dwelling older adolescents in India’ concluded that overweight, obesity, socioeconomic factors and higher education status were responsible for hyperglycemia in adolescents aged 15-19 years in India. We highlight that there is a significant prevalence of T2DM even in normal body mass index (BMI) and below normal BMI subjects, as mentioned in their study. There is a high prevalence of normal weight obesity in Indian adolescents which often gets missed due to a large population with normal BMI in the country. In this letter, we analyze the importance of measurement of central adiposity beyond routine BMI measurements.

Key Words: Normal weight obesity; Adolescents; Body mass index; Metabolic syndrome; Body composition; Visceral fat; Cardiometabolic risk

Core Tip: Normal weight obesity in adolescents can be a hidden risk factor for cardiometabolic diseases, emphasizing the need for healthcare professionals to assess body composition, beyond body mass index, to identify and manage this under-recognized entity effectively.

TO THE EDITOR

We keenly read the study published by Maheshwari et al[1] on the rise in the prevalence of obesity and hyperglycemia among Indian adolescents aged 15-19 years. The study utilized data from the NHFS-5, a nationally representative sample. The research identified that the major contributory determinants of type 2 diabetes mellitus (T2DM) were overweight/obesity, increasing age, higher level of education, and higher wealth index. However, what caught our attention in the article was table 2 (Table 1)[1], which shows the distribution of factors associated with T2DM in the study population. Of the 1382 adolescents with diabetes, it is notable that 1088 (78.7%) had a normal body mass index (BMI), 153 (11%) had a below-normal BMI, and 141 (10.2%) were overweight or obese. Understandably, the denominator of normal and thin BMI is large; therefore, the percentage of normal-weight individuals with T2DM is low, and the relative risk is not significant. Although obesity is a well-established risk factor for diabetes, we cannot ignore the large number of adolescents with normal BMI suffering from T2DM, which is a forerunner for life-threatening noncommunicable diseases. Overweight and obesity may be misinterpreted by the readers, who are likely medical professionals, as the sole metabolic risk factor (with other factors being related to socioeconomic status and education). This interpretation is potentially misleading and could encourage the use of BMI alone to screen for clinical risk factors for T2DM, omitting central obesity, which could be readily assessed using visceral adiposity metrics such as waist circumference and waist-to-hip ratio. This letter discusses current research findings and potential determinants of normal-weight obesity. Moreover, it provides concise recommendations for mitigating the risk factors associated with this condition, which constitutes a significant proportion of the adolescent population with T2DM, as observed in the study by Maheshwari et al[1].

Table 1 Distribution of factors associated with diabetes mellitus (previously and newly diagnosed cases), n (%)[1].

Variables	DM absent, n = 221556	DM present, n = 2359	Unadjusted RR (95%CI)	Adjusted RR (95%CI)
Age in years, mean (SD)	16.98 (1.40)	17.11 (1.40)	1.07 (1.02-1.11)a	1.09 (1.02-1.15)a
Sex
Male	105161 (98.87)	1168 (1.13)	Reference	-
Female	116395 (98.95)	1191 (1.05)	0.93 (0.83-1.04)
Respondents’ education
No education	7785 (99.24)	73 (0.76)	Reference	Reference
Primary education	12239 (98.95)	142 (1.05)	1.38 (0.97-1.96)	1.14 (0.74-1.75)
Secondary education	189093 (98.91)	1987 (1.09)	1.43 (1.07-1.91)a	1.31 (0.91-1.88)
Higher education	12414 (98.83)	156 (1.17)	1.53 (1.09-2.15)a	1.13 (0.73-1.76)
Religion
Hindu	98145 (98.95)	1006 (1.05)	Reference	-
Muslim	17820 (98.78)	210 (1.22)	1.17 (0.95-1.44)
Others	14248 (98.85)	151 (1.15)	1.10 (0.81-1.49)
Residence
Urban	49616 (98.88)	562 (1.12)	Reference	-
Rural	171940 (98.93)	1797 (1.07)	0.96 (0.84-1.11)
Wealth index
Poorest	52225 (99.05)	486 (0.95)	Reference	Reference
Poorer	54247 (98.86)	612 (1.14)	1.19 (1.01-1.41)a	1.22 (0.97-1.53)
Middle	47012 (98.86)	523 (1.14)	1.20 (1.01-1.42)a	1.21 (0.97-1.52)
Richer	38521 (98.89)	428 (1.11)	1.16 (0.98-1.39)	1.11 (0.88-1.41)
Richest	29551 (98.93)	310 (1.07)	1.12 (0.93-1.36)	1.19 (0.92-1.54)
Tobacco consumption
No	211095 (98.92)	2242 (1.08)	Reference	-
Yes	10087 (98.67)	115 (1.33)	1.23 (0.96-1.57)
Alcohol usage
No	217809 (98.91)	2332 (1.09)	Reference	-
Yes	3402 (99.12)	25 (0.88)	0.81 (0.47-1.38)
BMI
Normal	110800 (99.01)	1088 (0.99)	Reference	Reference
Thin	12659 (98.78)	153 (1.22)	1.24 (0.99-1.56)	1.24 (0.99-1.56)
Overweight/obese	8377 (98.13)	141 (1.87)	1.90 (1.50-2.40)b	1.85 (1.46-2.34)b
Health seeking behaviour in past 3 months
None	97890 (98.92)	993 (1.08)	Reference	-
Public facility	19697 (98.78)	242 (1.22)	1.14 (0.93-1.39)
Private facility	12261 (99.1)	128 (0.9)	0.84 (0.66-1.06)
Other	361 (99.4)	4 (0.6)	0.56 (0.18-1.73)

^aP < 0.05.

^bP < 0.001.

BMI: Body mass index; CI: Confidence interval; DM: Diabetes mellitus; RR: Rate ratio. Citation: Maheshwari V, Basu S. Prevalence of obesity, determinants, and its association with hyperglycaemia among community dwelling older adolescents in India. World J Clin Pediatr 2024; 13: 91638. Published by Baishideng Publishing Group.

Discussion

Normal weight obesity (NWO), a term introduced by De Lorenzo, is a recently recognized phenotype characterized by individuals who appear petite and possess a normal BMI yet exhibit a high body fat percentage, which correlates significantly with cardiometabolic illnesses. This phenotype is increasingly observed in Asians, particularly Indians, who show a high prevalence of T2DM and other metabolic disorders despite a comparatively lower proportion of obese adults as determined using BMI. Yet, this aspect is clinically under-recognized and under-researched among South Asians, especially Indians[2].

According to data from the diabetes prevention program in South India, of the 1147 adults at high risk of T2DM, up to 32% had NWO, 51% were overtly obese, and 17% were nonobese[3]. The prevalence of T2DM was significantly higher in the NWO group (19.7%) compared with 8% in the nonobese group, a finding also reported in the article by Maheshwari et al. in the adolescent age group.

The importance of raising awareness about NWO in children and adolescents, particularly those of Asian Indian descent, has been highlighted in a study conducted by Nawab et al[4] in a non-metropolitan North Indian city. This investigation showed an alarmingly high burden of central obesity (28.5%), which was almost double the burden of generalized obesity (14.6%), in school-going adolescent children. Nearly one-fourth of normal-weight adolescents exhibited central obesity. The finding of central obesity, which could shed more light on the potential mechanistic factors contributing to a large percentage of normal-BMI children developing T2DM in the study, was overlooked by Maheshwari et al[1] This observation emphasizes the significance of routine measurement of adiposity over BMI in this population at high risk of T2DM[5,6].

Potential determinants of NWO

Genetic factors: Of the various factors that determine the development of NWO, genetic variations in the form of polymorphisms are a key consideration[7]. Di Renzo et al[8] have identified single-nucleotide polymorphisms in various genes, including interleukin (IL)-1 receptor antagonist, methylenetetrahydrofolate reductase, IL-15 receptor α, IL-6, and tumor necrosis factor-alpha, which are highly prevalent in individuals with the NWO phenotype[8-11].

Nutritional deficiencies

Genetic factors, compounded by nutritional deficiencies, particularly in the intake of vitamins and minerals during childhood and adolescence, can affect glucose and lipid homeostasis. Deficiency of vitamin A, vitamin B, and vitamin D can impair metabolic processes and the rate of energy production, thus aggravating insulin resistance. Calcium, magnesium, and zinc deficiencies are known to slow down metabolism and lead to a proinflammatory state[12]. Fatigue related to iron deficiency can lead to a sedentary lifestyle, contributing to weight gain and exacerbating insulin resistance[13].

Birth weight

The metabolic impact of low birth weight was studied by Thomas et al[12] in a nonmigrant South Indian population. The participants exhibited impaired glucose tolerance, high diastolic blood pressure, and low lean body mass, all in the presence of normal body weight as adults. This finding highlights the connection between “small for gestational age” and the subsequent development of cardiometabolic risk factors.

Sex difference

A cross-sectional analysis by Marques-Vidal et al[13] involving over 5000 patients observed that women with NWO have a higher prevalence of dyslipidemia, hypertension, and fasting hyperglycemia compared with their lean counterparts. Conversely, NWO was nearly absent in men within the study population. Further research in this area may enhance our understanding of the mechanisms and rationales underlying sex differences in NWO.

Recommended measures to overcome NWO

To date, genetic polymorphisms are non-modifiable factors contributing to obesity. However, understanding the factors that lead to the development of NWO provides a unique window of opportunity for the healthcare framework. The role of intensifying lifestyle measures and discouraging sedentary behaviors in improving cardiometabolic outcomes in individuals with NWO has been demonstrated in a follow-up study conducted by Kapoor et al[14]. This observation also calls for policymakers and healthcare practitioners at various levels of infrastructure to enhance maternal and child nutrition and prevent micronutrient deficiencies.

CONCLUSION

Thus, NWO, a recognized high-risk phenotype for the development of T2DM and metabolic syndrome in adults, is also of equal concern among children and adolescents. A multidisciplinary approach is warranted for effective long-term risk reduction of metabolic syndrome in general and T2DM in particular.