Micro- and Macrovascular Complications in Early-Onset Type 2 Diabetes in Indians: Prevalence and Predictors in a Prospective Cross-Sectional Study.

Introduction

Diabetes mellitus ranks among the most common chronic conditions globally, with a great economic burden to global healthcare. Statistics from the 2021 IDF (International Diabetes Federation) Atlas indicate that one in every ten subjects aged between 20 and 79 years has diabetes, a condition that accounts for almost 11.5% of world healthcare costs ( 1 ). Over the years, an increasing incidence of early-onset type 2 diabetes mellitus (EOD) in individuals less than 40 years of age ( 2 , 3 ) has been noted. The global and regional prevalence of EOD cases was estimated at around 4–8% in the year 2021. Fifteen to twenty percent of all cases of EOD are reported from India ( 1 ). A study based in South India showed that the prevalence of T2DM among younger individuals had increased by 36% within a decade ( 4 ). In a study from North India, of 105 patients with onset between 18 and 35 years, T2DM and type 1 diabetes were equally prevalent (40% each) ( 5 ).

Previous research has shown that early-onset type 2 diabetes carries a higher risk of developing macro- and microvascular complications, as well as higher mortality, when compared to type 1 diabetes or late-onset type 2 diabetes (LOD) ( 6 ). Pathological processes, such as the increase in insulin resistance and decline in beta-cell function, progress more rapidly in EOD than in LOD ( 7 ). Consequently, these can lead to poor glycemic control, need for insulin at a younger age, and a higher risk of early complications related to diabetes. These patients may have increased morbidity and a lower quality of life ( 8 ). The TODAY Study Group concluded that those with youth-onset type 2 diabetes (average age of onset being 13 years) were more likely to develop diabetes-related comorbidities by the age of 30, especially those with poor glycemic control, dyslipidemia, and hypertension ( 9 ). A UK-based study reported that the rate of increase in microvascular and CVD-related complications with longer diabetes duration was higher for those diagnosed before the age of 40 years ( 10 ). In a retrospective study, a high prevalence of nephropathy, end-stage renal failure, and blindness, along with differences in metabolic profiles, was observed in Japanese individuals with EOD compared to the Caucasian population ( 11 ).

A study conducted in South India comparing early-onset (≤25 years) and late-onset (≥50 years) diabetes showed that young-onset T2DM was associated with a higher frequency of retinopathy (47.6 vs 31.0%). However, the prevalence of nephropathy was comparable ( 12 ). Another retrospective study from North India indicated that microvascular complications and coronary artery disease (CAD) were significantly more prevalent among subjects with LOD ( 13 ).

There have been only a few studies that have compared EOD and LOD ( 14 ). Indians developed diabetes at a younger age and had lower body mass index (BMI) than Europeans. Its pathophysiology is characterized by both insulin resistance and deficiency ( 4 , 5 ). In Indian subjects with diabetes, cardiovascular disease develops a decade or two earlier than in the Western population. Triple vessel CAD is more common, and mortality is higher in Indian patients ( 15 ).

Most previous studies of EOD have evaluated patients retrospectively, and patients have not been matched for duration of diabetes and gender with LOD. There is still a paucity of data on the clinical characteristics of patients with EOD compared to LOD. The purpose of this study was to determine the prevalence and severity of complications in patients with EOD (ages 18–39 years) and compare them with LOD (age 40 years and more) in the Indian population.

Materials and methods

Study design and subjects

This was a prospective cross-sectional, single-center study conducted at a tertiary care university hospital in Uttar Pradesh, North India. Consecutive adult patients (aged 18–80 years) with laboratory-confirmed T2DM who showed to the Endocrinology outpatient department (OPD) during the 2-year study period (September 2022 to August 2024) were recruited. A total of 1,304 subjects who visited the investigator’s diabetes OPD were invited to participate in the study. The study excluded individuals with a history of ketosis, type 1 diabetes, or pancreatic diabetes, as well as those taking medications that could induce hyperglycemia (such as steroids, pentamidine, or first- and second-generation antipsychotics). Pancreatic diabetes was considered secondary to chronic calcific pancreatitis, which is characterized by pancreatic parenchymal and/or ductal calcifications, Cambridge stage 3–4 changes on cross-sectional imaging, or histological evidence of chronic pancreatitis ( 16 ). Subjects with neuropathy caused by factors other than diabetes (vitamin B12 deficiency, multiple myeloma, hypothyroidism, or chronic inflammatory demyelinating polyneuropathy) and those diagnosed with chronic liver disease were not eligible for study participation. One hundred six subjects were excluded from the study for the following reasons: 33 had fibrocalcific pancreatic diabetes, 10 had type 1 diabetes, 41 had impaired glucose tolerance, 11 had cirrhosis, and 10 had gestational diabetes.

Out of the 1,198 T2DM subjects, a total of 800 subjects were enrolled, with 400 in the EOD group (age of onset <40 years) and 400 in the LOD group (age of onset ≥40 years) ( Fig. 1 ). Participants were matched for the duration of diabetes (<5 years, 5–10 years, 10–15 years, and >15 years) and gender. The subjects who participated had a similar age (median 52 years, range 18–80 years vs median 50 years, range 18–80 years), sex ratio (male/female = 1.7 vs 1.4), and duration of diabetes compared to non-responders (the term ‘non-responders’ referred to participants who met the inclusion criteria but chose not to participate in the study or did not complete the required investigations despite three separate attempts).

All subjects were enrolled in the study after signing an informed consent form. The participants’ privacy rights were strictly protected. The study was conducted as per the Helsinki Declaration of 1975 (as revised in Fortaleza, Brazil, October 2013). The Institutional Ethics Committee of the Institute approved the study and research protocol (IEC code: 2019-195-DM-113).

Study protocol and data collection

A detailed study proforma was used to record the subjects’ demographic information, socioeconomic status (modified Kuppuswamy socioeconomic scale 2023), and anthropometric measurements (height, weight, BMI, and waist circumference) ( 17 ). History of diet, exercise, family history of diabetes, history or symptoms of micro- and macrovascular complications, diabetes duration, and its management was recorded. History of hypertension, dyslipidemia, smoking habits, and use of alcohol was recorded.

Body weight was recorded in kilograms with patients dressed in light clothing and barefoot. Height was measured using a stadiometer in centimeters without shoes or head coverings. Waist circumference was taken using a non-stretchable tape at the midpoint between the iliac crest and the lower rib margin, following a normal exhalation. BMI was calculated using the formula: BMI = weight (kg)/height (m) 2 . Blood pressure (BP) was measured after the administration of the questionnaire. BP was recorded in the sitting position in the right arm using a mercury sphygmomanometer (Diamond, Industrial Electronic and Allied Products, India). The measurement was repeated after 5 min, and the second reading was used for analysis. The diagnosis of hypertension was made according to the JNC VII criteria ( 18 ).

Screening for neuropathy

Diabetic peripheral neuropathy (DPN)

Patients were tested for distal symmetric DPN by a single investigator. DPN was evaluated using the neuropathy symptom score (NSS) and neuropathy disability score (NDS), following the specified protocol ( 19 ). Both the NSS and NDS have been validated against electrodiagnostic studies, ensuring their reliability in diagnosing diabetic peripheral neuropathy ( 20 ).

DPN was diagnosed when subjects had moderate to severe signs regardless of symptoms, or when mild signs were accompanied by moderate to severe symptoms.

Assessment of vibration perception threshold (VPT) using biosthesiometer

Vibration sensation was evaluated as the VPT using a biosthesiometer (Dhanshree Lab, Mumbai) by a single observer following a standardized protocol. VPT measurements were taken at the distal plantar surface of both the right and left great toes. Impaired VPT was diagnosed if the value for the great toe exceeded the mean plus two standard deviations (>16 V), a threshold established separately for non-diabetic subjects based on data from 50 healthy controls aged 25–45 years ( 21 ).

Monofilament testing

The test was conducted using Semmes-Weinstein monofilaments (5.07/10 g) and performed at ten sites: the dorsal surface (between the base of digits 1 and 2), ventral surface (digits 1, 3, and 5), metatarsal heads (1, 3, and 5), medial and lateral midfoot, and the heel. Each site was tested three times: twice using the monofilament and once as a dummy test. If the patient missed at any site on more than one occasion, it was considered abnormal at that site. If the patient was unable to perceive the filament at two or more of the ten sites (value ≤8), the result was considered abnormal ( 22 ).

Screening for nephropathy

Nephropathy was assessed by urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Patients collected an overnight urine sample after being instructed to avoid strenuous exercise. Urine was screened for white blood cells; samples with elevated counts were discarded and retaken post-treatment. If hematuria was detected, underlying causes were evaluated, and patients with permanent conditions were excluded. In cases of initial albuminuria, urine samples were re-collected after 3 months to confirm persistence ( 23 ).

Screening for retinopathy

Patients were evaluated for retinopathy either by fundus examination in dilated pupils or fundus imaging. Fundus examination was done by +90 D slit lamp biomicroscopy, and standard ETDRS 7-field color fundus photographs were taken by a digital fundus camera (Carl Zeiss FF 450 plus IR; Zeiss Meditech, USA). Severity of retinopathy and macular edema was determined using the International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scale (referred to hereafter as the International Classification) ( 24 ).

It categorized diabetic retinopathy into five distinct levels (no apparent retinopathy, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy, severe non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy) based on findings observable during dilated ophthalmoscopy.

Macrovascular complications

Coronary artery disease (CAD)

The diagnosis of CAD was based on clinical history of angina pectoris and/or previously treated myocardial infarction (MI), and previous investigations including electrocardiography (ECG), 2-dimensional echocardiography (2D-ECHO), and coronary angiography. Other than diagnosed cases, patients with symptoms or abnormal ECG findings underwent 2D-ECHO by a cardiologist (RSA and NG). 2D-ECHO was performed using a GE Vivid E9 XD machine ( 25 ). In the presence of any abnormality in 2D-ECHO, further workup was done by the cardiologist for confirmation of diagnosis.

Peripheral vascular disease (PVD)

All patients with a history of intermittent claudication or rest pain, or non-palpable peripheral pulses were suspected to have PVD. The ankle-brachial index (ABI) was measured in all patients. The ABI (EMCO Meditek Pvt. Ltd, India) was calculated using the ratio of the highest ankle pressure signal between the dorsalis pedis and posterior tibial arteries of the right and left ankles to the highest brachial pressure signal from the left and right arms. ABI was considered abnormal when <0.9 or >1.4 ( 26 ). For confirmation, a lower limb arterial Doppler (Aixplorer Ultrasound system, Supersonic Imagine, France) with a linear-array probe was performed by a single radiologist. The diagnosis of PVD was made when the Doppler indicated monophasic blood flow.

Cerebrovascular accidents (CVA)

Diagnosis was based on history, clinical examination, or history of physician-treated CVA. It was documented by objective evidence from computed tomography or magnetic resonance imaging records. Atherosclerotic cardiovascular disease (ASCVD) refers to all clinical conditions of atherosclerotic origin, including acute coronary syndrome (ACS), those with a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral artery disease (PAD), including aortic aneurysm ( 27 ).

Definitions

Diabetes mellitus was defined as per the American Diabetes Association (ADA) Criteria: symptomatic subjects with a random plasma glucose ≥200 mg/dL, or fasting plasma glucose ≥126 mg/dL, or plasma glucose ≥200 mg/dL after 2 h of the oral glucose tolerance test, or having pre-existing T2DM ( 28 ).

Population-specific (Asian) cut-offs for BMI were used. BMI was categorized as follows: normal BMI 18.0–22.9 kg/m 2 , overweight between 23.0 and 24.9 kg/m 2 , and obesity was classified as a BMI greater than 25 kg/m 2 . Central obesity was defined as waist >90 cm in males and >80 cm in females ( 29 ).

Lipid profiles were considered abnormal if: TC ≥200 mg/dL, TG ≥150 mg/dL, LDL-C ≥100 mg/dL, non-HDL-C ≥130 mg/dL, and HDL-C ≤40 mg/dL in men or ≤50 mg/dL in women. Metabolic syndrome and dyslipidemia were defined according to the Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), i.e., NCEP-ATP ΙΙΙ criteria ( 30 , 31 ).

The normal urinary albumin excretion ratio (UACR) was defined as less than 30 mg of albumin per gram of creatinine. When albuminuria ranged between 30 and 300 mg/g creatinine, it was classified as moderately high, while it was considered severely high when albuminuria was 300 mg/g creatinine or above. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were used to determine the estimated glomerular filtration rate (eGFR) ( 32 ). An estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 was considered abnormal ( 23 ). If there was no other evidence of causes of kidney damage, diabetic kidney disease or nephropathy was clinically diagnosed by the presence of albuminuria and/or a decreased eGFR ( 33 ).

ECG was considered abnormal if there was evidence of old MI, abnormal ST-T changes, and left ventricular hypertrophy. Evidence of MI was regarded as positive if significant Q waves were present in more than one consecutive lead. ST-T segment abnormality was noted as present if either of the following was detected in the absence of bundle branch blocks and left ventricular hypertrophy: ST segment depression or elevation of at least 1 mm, or inverted T wave in any lead where the QRS complex had a net positive deflection ( 34 ). Left ventricular hypertrophy was coded as present or absent according to Romhilt and Estes’ criteria ( 35 ).

Two-dimensional color-flow echocardiography determined cardiac size, left ventricular hypertrophy, ejection fraction, and regional wall motion abnormality (RWMA). The presence of RWMA was taken as hard evidence of CAD ( 27 ). Coronary angiography was performed whenever required for diagnostic confirmation and for therapeutic purposes. Obstructive CAD was defined as the presence of one or more epicardial coronary arteries with greater than 50% diameter stenosis.

Analytical methods

Fasting blood samples from study subjects were collected for plasma glucose, creatinine, glycosylated hemoglobin (HbA1C), and lipid profile. Blood samples for plasma glucose were collected in fluoride vials, HbA1c in EDTA vials, while samples for other analytes (lipid profile and serum creatinine) were collected in plain vials. A morning urine sample was collected for estimation of urinary albumin-to-creatinine ratio.

Serum biochemistry (lipid profile, plasma glucose, creatinine) and urinary albumin and creatinine were performed on an auto-analyzer (Imola Randox, Randox Laboratories Ltd, USA). LDL cholesterol was calculated by using Friedewald’s equation. Urinary microalbumin was measured by an immunoturbidimetric method, while urinary creatinine was assessed by the modified Jaffe’s method. HbA1C was measured by high-performance liquid chromatography method (Bio-Rad Laboratories, USA).

Statistics

Normality of data was tested using the Kolmogorov–Smirnov test. Continuous variables were showed as median (interquartile range (IQR)), and categorical variables were reported as frequency and percentage. Mann–Whitney U test was used for comparison of non-parametric data. The chi-square test was used to assess differences in categorical variables.

Trends were calculated using chi-square tests to evaluate the statistical significance of microvascular and macrovascular complications within the duration of diabetes.

Univariate logistic regression analysis was used to identify risk factors for microvascular and macrovascular complications. The continuous variables were categorized into units as follows for analysis: age: 5 years, duration of diabetes: 5 years, BMI: 2 kg/m 2 , height: 5 cm, plasma glucose, TC, non-HDL-C, TG, and LDL-C: 10 mg/dL, and HDL-C: 5 mg/dL. The independent variables tested included age of onset of diabetes, duration of diabetes, gender, BMI, HbA1c, hypertension, plasma glucose, non-HDL cholesterol, triglycerides, and HDL cholesterol. All variables were tested by backward multivariate logistic regression to determine the independent associations with peripheral neuropathy, retinopathy, nephropathy, and ASCVD. A P value < 0.05 was considered significant. Statistical analyses were performed using the SPSS software package (version 23.0; SPSS Inc., USA).

Results

Patient characteristics

A total of 800 subjects were included in the study, with 400 in each group: early-onset and late-onset T2DM. The baseline characteristics of subjects stratified by onset (early or late) of T2DM are shown in Table 1 . The median age of onset of diabetes was 35 years (interquartile range (IQR), 31–37) in early-onset T2DM and 48 years (IQR, 43–54) in late-onset T2DM subjects. There was a male (63%) preponderance in the study. Sixty-eight percent of the patients were of an upper or upper-middle socioeconomic class. There was no significant difference in overall socioeconomic status between the EOD and LOD patient groups. Family history of diabetes in first-degree relatives was significantly higher in EOD compared with LOD patients (308 (77%) vs 240 (60%), P < 0.001).

Eighty percent of the EOD group was overweight or obese. There was no difference in BMI between EOD and LOD groups ( P = 0.72). The prevalence of metabolic syndrome and abdominal obesity was found in 85 and 71% of the EOD group, figures similar to those with LOD. In patients with EOD, 43% had hypertension within 5 years of diabetes and 58% within 10 years. However, the prevalence of hypertension was higher in LOD vs EOD (54 vs 37%) ( Table 1 ). Patients with EOD had significantly higher non-HDL cholesterol and triglycerides, and lower HDL cholesterol ( Table 1 ).

Glycemic control

The median plasma glucose levels were similar in the EOD and LOD groups at the first visit to our outpatient clinic. However, HbA1c levels at the first visit were significantly higher in patients with EOD (7.9% (IQR, 6.9–9.2%) vs 7.7% (IQR, 6.8–8.9%), P < 0.05). A higher proportion of subjects with EOD required more than three medicines for glycemic control (58 vs 50%, P < 0.05) and insulin (28 vs 20%, P < 0.01) at the first visit ( Table 1 ). Sixty-two percent of EOD patients required insulin after 15 years of diabetes duration, compared to 41% of the LOD group ( P < 0.05).

Complications

The relationship between early- and late-onset T2DM and their complications is shown in Table 2 . A significantly higher proportion of LOD patients had neuropathy ( P < 0.001) and ASCVD ( P < 0.001). However, there was no difference in the occurrence of retinopathy or nephropathy between the two groups. At least one microvascular complication was present in 69% of subjects with EOD and 75% of those with LOD ( P < 0.05) ( Table 2 ). All three microvascular complications were observed in 8% of patients with EOD and 10% with LOD, respectively ( Fig. 2 ). Abnormal VPT by biothesiometer was detected in 45% of EOD and 67% of the LOD group ( P < 0.001).

In EOD, 27% of individuals had retinopathy, with 6% having severe NPDR or PDR ( Table 2 ). In addition, a higher number of LOD patients had low eGFR (21.0 vs 12.2%, P < 0.01), although no difference in the frequency of albuminuria was observed. One-third of EOD participants had nephropathy, and 25% had it within 5 years of diagnosis. Among subjects with nephropathy, 34% had retinopathy, with no difference between early- and late-onset groups. In EOD, the proportion of subjects with atherosclerotic cardiovascular disease (ASCVD) was higher in the presence of nephropathy (15 vs 7%, P < 0.05).

When both groups were further compared based on the duration of diabetes, it was found that in the 5–10-year diabetes duration group, the LOD group had a significantly higher prevalence of neuropathy, nephropathy, and ASCVD, while no significant difference was observed for retinopathy ( Table 3 ).

A significant rise in microvascular complications was noted in both EOD and LOD groups ( Fig. 3 ) with increasing duration of diabetes. However, a significant increase in the risk of macrovascular complications with increasing diabetes duration was observed only in early-onset T2DM ( P < 0.05) (Supplementary Table 1 (see section on Supplementary materials given at the end of the article)).

At a median age of 37 years and duration of 5 years, 18% of early-onset T2DM patients had developed retinopathy, while one-fourth had nephropathy. A similar prevalence of these complications was observed in late-onset T2DM patients at a median age of 55 years ( Fig. 4 ).

Multivariate analysis

Table 4 displays the findings of a multivariate logistic regression analysis. Every 5-year increase in diabetes duration raised the odds of peripheral neuropathy, retinopathy, and nephropathy. Female gender, LOD, and presence of retinopathy were also significant contributors to peripheral neuropathy. Nephropathy was a significant predictor of retinopathy, while age of onset of diabetes and retinopathy were positively associated with nephropathy. LOD, smoking, and nephropathy were significant predictors of ASCVD. In addition, non-HDL cholesterol initially appeared to negatively predict the risk of ASCVD; however, after adjusting for the use of hypolipidemic medications, no significant association was found.

Discussion

We noted that the EOD group was characterized by poor glycemic control, increased metabolic abnormalities, and rapid progression of chronic complications at a young age. While the prevalence of microvascular complications, such as diabetic retinopathy and nephropathy, was similar in both groups, this study highlights the significant burden of microvascular disease in patients with EOD. This study also documented that subjects with EOD had higher complication prevalence than those with LOD at identical ages.

In our study, the prevalence of retinopathy in EOD was 27%, with 6% having severe NPDR or PDR. Retinopathy was significantly associated with duration of diabetes but not with the age at onset. Previous studies have reported a wide range of retinopathy prevalence in EOD (4–40%), largely influenced by study design and patient characteristics ( 36 , 37 , 38 ). In contrast, Song et al. observed that individuals diagnosed before the age of 40 years with >10 years of diabetes duration had a higher prevalence of retinopathy compared to those diagnosed after 40 years. They concluded that age of onset was not an independent predictor; rather, poor glycemic control and disease duration were the key determinants ( 39 ).

Nephropathy in EOD is of great concern since it can lead to chronic renal failure and is a risk factor for ASCVD at an early age. In our study, it was of concern that one-third of participants with EOD had nephropathy, and one-fourth had nephropathy within 5 years of diagnosis. A similar prevalence of nephropathy (up to 25% at diagnosis, increasing to 28–42% within 5 years) has been reported in the Western literature ( 36 , 40 ).

The presence of nephropathy increases the risk of retinopathy, with previous studies suggesting a retinopathy prevalence of up to 77% in patients with nephropathy ( 41 ). Consistently, we observed a higher rate of retinopathy among individuals with nephropathy: 32% in EOD and 33% in LOD compared to 23 and 22%, respectively, in those without nephropathy. Although hypertension, a key risk factor for nephropathy, was present in 65% of study subjects, a notable proportion (approximately one-third) remained untreated, which may be a contributory factor.

We found a significantly higher prevalence of peripheral neuropathy, with higher disability scores and abnormal VPTs, in the group with LOD. This may be due to advancing age, which previous studies have also identified as a contributing factor to neuropathy ( 12 ). Such trends could place a substantial strain on the economy ( 42 ). Logistic regression analysis identified female gender, longer duration of diabetes, and the presence of retinopathy as independent predictors of peripheral neuropathy, consistent with prior reports ( 10 , 43 ).

ASCVD was more prevalent among patients with LOD; however, it was notable that 9% of individuals in EOD already had ASCVD, which would expectedly increase with age ( 44 ). Numerous recent studies emphasize the heightened CVD risk in CKD, with decreased eGFR and increased albuminuria being independent predictors of increased ASCVD risk, as well as all-cause and cardiovascular mortality. This could be because of endothelial dysfunction, oxidative stress, and inflammation. In line with this, multivariate analysis in our study also identified nephropathy as a significant predictor of ASCVD ( 45 , 46 ). A post hoc analysis of the ADVANCE study found that patients with UACR >300 mg/g and eGFR <60 mL/min/1.73 m 2 had a 3.2-fold higher cardiovascular risk ( 44 ).

Importantly, our data demonstrated that by age 54 years, individuals with EOD exhibited cardiovascular risk factors (overweight or obese, dyslipidemia, hypertension) comparable to those of LOD participants at age of 67 years. Supporting this, a 7-year prospective study from Hong Kong reported that, after adjustment for age, patients with young-onset type 2 diabetes had a 30–50% greater risk of cardiovascular disease relative to those with LOD ( 47 ). In addition, Rhodes et al. estimated that patients with EOD are likely to develop severe chronic complications by their 40 s, with a reduction in life expectancy of 8–15 years ( 48 ).

In the current study, the duration of diabetes was recognized as the main risk factor for developing microvascular disease. In the Australian National Diabetes Audit, Nanayakkara et al. reported that for every 1-year increase in diabetes duration in adults, the odds ratio of developing microvascular complications increased by 11% ( 49 ). Participants with a longer duration of diabetes experience chronic hyperglycemia, leading to oxidative stress, vascular damage, and beta-cell exhaustion ( 7 , 50 ).

In our study, three-quarters of the participants with early-onset T2DM had poor glycemic control at the time of presentation to the clinic. Similarly, 50% subjects had high non-HDL cholesterol, and half had high triglycerides. In addition, three-quarters of patients in the EOD group had low HDL cholesterol. Studies from South India and Southeast Asian countries have similarly reported that subjects with EOD had worse glycemic control and dyslipidemia as compared to LOD ( 12 ). A combination of hyperglycemia and hyperlipidemia (glucolipotoxicity) together could cause severe damage to beta cells ( 51 ).

Obesity, hypertension, and dyslipidemia were common components of metabolic syndrome frequently observed in EOD. In our study, 80% of participants with both EOD and LOD were overweight or obese. However, other studies showed that a higher proportion of EOD patients (80–92%) were obese compared to 56% of older individuals, showing an inverse linear relationship between BMI and age of onset ( 52 , 53 ).

In our study, 43% of patients with EOD developed hypertension within 5 years of diagnosis, rising to 58% after 10 years. These findings are similar to those reported by Benhalima et al. and the TODAY Study Group ( 40 , 54 ). Our findings revealed a high prevalence of dyslipidemia in early-onset T2DM patients. The high prevalence of obesity, hypertension, dyslipidemia, nephropathy, retinopathy, and peripheral neuropathy highlights the need for screening for complications at the onset of EOD ( 55 ).

In view of the rising prevalence of EOD, the ADA 2022 guideline advocates decreasing the age for screening for prediabetes and diabetes from 45 to 35 years ( 56 ). These findings emphasize the necessity of screening at-risk young adult populations for type 2 diabetes, as early intervention could potentially reverse the condition.

The strength of this study lies in its prospective design for recruitment and comparison of groups matched for diabetes duration and gender. Screening for complications was done in a uniform manner for all participants in the study. Most previous studies have focused on the impact of EOD and T1DM on chronic complications. However, there are a limited number of studies comparing diabetes complications between EOD and LOD. However, our study has some limitations. The results may not be generalizable, as it was a single-center study involving subjects who showed to a tertiary care hospital. Due to the cross-sectional nature of the study, it was challenging to determine the relative contributions of multiple predictive factors to diabetes complications. A single HbA1c and plasma glucose measurement taken at the first hospital visit may not adequately reflect a patient’s overall glycemic control throughout the course of diabetes.

In conclusion, patients with EOD had poor glycemic control, hypertension, dyslipidemia, and metabolic syndrome, and a high prevalence of both micro- and macrovascular complications. The prevalence of nephropathy and retinopathy, including their advanced manifestations, was similar in both EOD and LOD, implying an increasing burden from these complications. While ASCVD was lower in EOD, the poor glycemic control, high prevalence of hypertension, dyslipidemia and obesity suggest that these will increase with follow-up. Patients with EOD need to be regularly screened for their glycemic control and diabetic complications, and rigorous preventive measures need to be adopted.

Supplementary materials

Declaration of interest

The authors have no relevant financial or non-financial interests (including relationship) to disclose.

Funding

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution statement

AS, DS, AG, RSA, MMK, APS, NG, EB, and SCY contributed to the conception and design of the study, acquisition, analysis, and interpretation of data, drafted the article, revised it critically for important intellectual content, approved the final version to be submitted, and agreed to be accountable for all aspects of the work.

Ethics statement

All subjects were enrolled in the study after signing an informed consent form after a full explanation of the purpose and nature of all procedures used. The participants’ privacy rights were strictly protected. The study was conducted as per the Helsinki Declaration of 1975 (as revised in Fortaleza, Brazil, October 2013). The Institutional Ethics Committee of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, approved the study and research protocol (2019-195-DM-113, dated December 29, 2019, amended on July 20, 2023).

Acknowledgments

We thank laboratory technicians Shahida Bano and Pooja Tripathi for their assistance in doing the ankle brachial index (ABI).

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