The Indian Obesity Paradox- Low in Muscle, High in Fat

The January 2004 issue of The Lancet had two very interesting publications relevant to body composition of Indians. The first was an interesting clinical picture titled the ‘Y-Y paradox’. This article showed that despite having the same body mass index (BMI), Dr Yagnik, an Indian physician, had more than twice the body fat percentage of Dr Yudkins from the UK.[1] The second publication was the WHO Expert Consultation regarding appropriate BMI for Asian populations recognizing the higher metabolic risk despite the lower BMI.[2] While these observations focused mainly on the body fat, the corollary was that Asians should have a comparatively lower fat-free mass (including lean mass). With the availability of body composition assessment using dual energy X-ray absorptiometry (DXA) and bioelectric impedance, several Indian studies confirmed a lower muscle mass in Indians, thereby establishing the unique obesity paradox of high fat and low muscle.[3] When this muscle mass is significantly low it is called sarcopenia. The coexistence of low muscle (sarcopenia) and high fat (obesity) was later appropriately termed as sarcopenic obesity.

Sarcopenic obesity (SO) is an entity that although well recognized, does not have a clear, universally accepted definition. A combination of obesity diagnosed by BMI cut-offs proposed by WHO for South Asians and the Asian Working Group for Sarcopenia (AWGS) criteria has been used in various studies from India.[4] The AWGS criteria look at muscle mass, muscle strength as well as physical performance. Recently, the Asia-Oceania Association for the Study of Obesity (AOASO) and the International Association of Gerontology and Geriatrics Asia/Oceania Region (IAGG-AOR) have proposed a three-step algorithm focusing on screening, diagnosis and management of SO.[5] This algorithm proposes simpler tests such as calf circumference, SARC-F questionnaire, and Finger ring test (for sarcopenia) along with BMI and waist circumference for screening of SO. Assessments of muscle mass and tests for muscle function are reserved for confirmation of the diagnosis. A similar consensus document has also been published by the South Asian Working Action Group on SARCOpenia.[6]

The prevalence of SO in India has been reported variably in different studies. The most notable are the estimates based upon the Longitudinal Ageing Study in India (LASI), which is a nationally representative survey over 73,000 older adults. An analysis of the first wave of LASI (2017–18) reported the prevalence of SO to be around 8%.[7] Further, in females and in those living in urban areas, the prevalence was as high as 14%. Data from the Sarcopenic Obesity-Chandigarh Urban Bone Epidemiological Study (SO-CUBES) showed that the prevalence of SO in community-dwelling healthy adults ranged from 5.4% to 6.3% (depending upon whether BMI or DXA-derived fat mass percent was used to define obesity).[8] While in the SO-CUBES, all patients with SO were above 65 years of age, the LASI data showed that even in the 45–54 year age, 6.4% had SO, indicating that this condition is not limited to the elderly. There seems to be limited data on SO in younger populations and this is an area that needs further investigation.

The prevalence of SO in diabetes appears to be much higher. In this issue, Salman et al.[9] the report prevalence of SO in persons with type 2 diabetes mellitus from a hospital in North India. Their study employs DXA for body composition assessment. They have reported an alarmingly high 44% prevalence of SO. However, this study was from a single tertiary care hospital, and more than a fifth of the participants had HbA1c above 9%. Another study from Gujarat, found that the prevalence of SO in older individuals living with diabetes was as high as 30.7%.[10] This high prevalence in persons living with diabetes is alarming.

The risk factors for SO are a combination of genetics and lifestyle factors. Decreased physical activity appears to be a strong risk factor for SO, as suggested by the Korea National Health and Nutrition Examination Survey data.[11] The presence of low muscle mass may itself be a strong contributory factor. Because muscle mass decreases with aging, a person with initially low muscle mass will rapidly become sarcopenic as their age increases. This sarcopenia will in turn, lead to reduced physical activity, leading to obesity. Dietary factors are also important for SO. A Korean study indicated that poor quality diet and inadequate protein intake was associated with SO, especially in women.[12] A lacto-ovo-vegetarian diet appears to reduce the risk of developing SO.[13] An association between self-reported long sleep duration and SO has been reported but this may indicate that frail older adults are spending more time in bed.[14] A novel risk factor for sarcopenia could be glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. The GLP-1 RAs have rapidly gained the forefront in pharmacotherapy of obesity due to the profound weight loss these drugs can achieve. This weight loss, like weight loss from any intervention, includes loss of lean body mass to the tune of 40% of the total weight loss.[15] In the typical Indian patient with high fat and low muscle, significant weight loss with GLP-1 RA therapy can cause a substantial reduction in the muscle mass, resulting in sarcopenia. Since some amount of residual obesity will persist despite the GLP-1 RA therapy, such a patient will then fit the label of SO. Therefore, efforts to maintain muscle mass must be taken along with GLP-1 RA therapy.

Sarcopenic obesity is not just an innocuous coincidence. It has far-reaching health consequences. It increases the risk of lifestyle disorders. Longitudinal data from China indicate that persons with sarcopenic obesity had a higher rate of progression from normoglycemia to diabetes as compared to individuals with either sarcopenia or obesity alone.[16] Similarly, data from Korea indicate a higher prevalence of diabetes in those with SO.[12] An association between SO and insulin resistance and inflammation has been reported.[17] The risk for dyslipidaemia is also higher in men with SO as compared to those with obesity or sarcopenia alone.[18]

In patients already affected by diabetes, SO worsens several complications. A retrospective cohort study from Japan found that in people living with diabetes, those with SO were significantly associated with incident cardiovascular disease even after adjusting for confounders.[19] A strong association between SO and left ventricular diastolic dysfunction has also been observed.[20,21] The risk of albuminuria in persons living with diabetes is also higher in those with SO.[22] These complications increase the mortality risk with SO.

Data from Japan indicates an almost 3-fold increase in mortality risk with sarcopenic obesity in persons living with diabetes.[23]

Apart from diabetes, the presence of SO appears to be a strong risk factor for non-alcoholic fatty liver disease, with both low muscle mass and muscle function showing independent association with NAFLD. The risk with SO was higher than that seen with sarcopenia or obesity alone.[24] Similar findings were reported earlier in a study from Korea and China, indicating a strong association between NAFLD and SO.[25,26]

The impact of SO is not limited to metabolic disorders. Individuals with sarcopenic obesity appear to have a greater deterioration in physical functions as compared to those with sarcopenia alone.[27] In a study, SO was associated with depressive symptoms in persons between 65 and 74 years of age.[28] SO was also found to be associated with impaired cognitive function, especially in the memory and language domains.[29] A study from Korea found that even at comparable body weights, the association between sarcopenic obesity and knee osteoarthritis was stronger than that for non-sarcopenic obesity.[30] Sarcopenia is associated with gastroesophageal reflux disease, and SO may be an independent predictive factor for erosive reflux disease.[31] Similar findings have been reported in another study.[32] An association between SO and gastric cancer has also been reported, indicating that SO may be a novel risk factor for gastric carcinogenesis.[33]

Recent data indicate that there is a link between SO and osteoporosis. Men, but not women, with sarcopenic obesity, A lower hip and whole-body bone mineral density (BMD) has been observed in males with SO.[34] A study from Chandigarh, India, showed that patients with sarcopenic obesity and type 2 DM had worse bone quality as assessed by volumetric HR-pQCT.[35] SO has also shown a significant association with fall risk in a study from China.[36] Similarly, a study from Turkey reported both increased fall risk and a poor health-related quality of life score in people with SO.[37] Together, impaired bone quality and increases fall risk can contribute to fractures, thereby multiplying the adverse health outcomes related to SO.

Considering the myriad adverse consequences of SO, efforts have been made to find effective treatments for SO. Exercise with nutritional supplementation led to a reduction in body fat and improved physical performance in a randomized controlled trial from Japan. However, no increase in muscle mass was observed.[38]

A meta-analysis of non-pharmacological interventions, primarily resistance exercise, reports that such interventions have shown efficacy in improving body composition, muscle strength (grip strength and knee extension strength), and gait speed.[39] The adherence to nutrition and exercise interventions for SO has been an area of concern. A meta-analysis looking at adherence and dropout rates reported that most studies in this domain do not report adherence data, and the overall dropout rate of 9% may be an underestimate.[40] This poor adherence, as well as difficulty in administering exercise programs, has spawned interest in other treatment modalities. Whole body-electromyostimulation has been studied and appears to have beneficial effects on muscle mass and function in elderly females.[41] Epicatechin, a polyphenol found in tea leaves and several fruits, appears to have an inhibitory effect on myostatin. Thus, it may be beneficial in sarcopenic obesity but clinical studies are lacking.[42] Pharmacological treatments to address SO are limited at present. Bimagrumab, a monoclonal antibody to the activin type II receptors, has shown potential in improving muscle mass in patients with sarcopenia in a few studies, while other studies report no improvement.[43,44] It has also been studied in preventing muscle loss seen with GLP-1RA therapy.[45] While this drug does appear to improve muscle mass, improvement in strength and physical performance was inconsistent in studies. A trial studying a combination of trevogrumab and semaglutide in preserving muscle mass during weight loss is underway, and the interim results have shown some benefit.[46] Other drugs inhibiting the myostatin/activin pathway such as domagrozumab, and landogrozumab have also been investigated for conditions like Duchenne muscular dystrophy, but studies in sarcopenia are lacking.[46] A novel unimolecular peptide tetra-agonist targeting GLP-1, GIP, glucagon, and amylin receptors (PTT-A) has shown potential in causing significant fat loss, while preserving lean mass.[46] Another molecule, the sirtuin 1 activator, SRT2104, appears to mimic the effects of exercise on muscle thereby benefiting muscle mass and potentially muscle strength.[47] Selective androgen receptor modulators (SARMs), including enobosarm may also increase muscle mass in cancer cachexia, but data have been conflicting.[48] It is important to note that most, if not all the studies, have been done in patients with sarcopenia, and very little is known about the response to these treatment in SO.

As India reels under the onslaught of lifestyle disorders, SO is not so obvious but a serious condition. It not only has the potential to amplify the morbidity and mortality from lifestyle disorders but can also independently affect health and worsen quality of life. As the Indian population begins to age gradually, SO prevalence is slated to increase. An elderly population, with this Indian obesity paradox would be the worst suffers in that case. Urgent efforts to address current as well as future SO, essentially by promoting resistance training and a healthy diet, are the need of the hour.

Declaration on use of AI

No AI was used in writing of this manuscript.