Type 2 diabetes mellitus (T2DM) is a global health crisis, with the International Diabetes Federation (IDF) reporting 463 million adults aged 20-79 affected in 2019, projected to rise to 700 million by 2045[1]. India, dubbed the “diabetes capital of the world,” had 77 million cases in 2019, with projections of 101 million by 2030[2]. This escalation is driven by urbanization, sedentary lifestyles, and genetic predispositions, necessitating preventive strategies[3]. Prediabetes, defined by the American Diabetes Association (ADA) as fasting blood sugar (FBS) of 100-125 mg/dL, 2-hour postprandial blood sugar (PPBS) of 140-199 mg/dL, or HbA1c of 5.7-6.4% [4], is a critical intermediary state. Approximately 35% of individuals with impaired glucose tolerance (IGT) progress to T2DM, with a five- to six-fold increased risk [5].

Microvascular complications, such as diabetic nephropathy (marked by microalbuminuria) and retinopathy, often emerge during prediabetes[6]. Microalbuminuria, with a urine albumin excretion rate (UAER) of 30-300 mg/day [7], signals endothelial dysfunction and heightened cardiovascular risk [8]. Retinopathy, detectable via fundoscopy, may manifest at prediabetic glucose levels, challenging current diagnostic thresholds [9]. These complications likely share pathophysiological mechanisms, including chronic hyperglycemia, oxidative stress, and inflammation[10]. This study aims to estimate the prevalence of microalbuminuria and retinopathy in prediabetic individuals and investigate their association, providing evidence to support early intervention strategies.

Study Design and Population

This cross-sectional study was conducted at ASRAM Hospital, Eluru, Andhra Pradesh, from June 2021 to Mar 2025. A total of 100 prediabetic patients were enrolled, comprising 58 males and 42 females, aged 30-79 years. Participants were recruited from outpatient (76) and inpatient (24) settings. Inclusion criteria included FBS of 100-125 mg/dL or HbA1c of 5.7-6.4%, confirmed by repeat testing. Exclusion criteria encompassed overt T2DM (FBS ≥126 mg/dL or HbA1c ≥6.5%), chronic kidney disease, hypertension, autoimmune disorders, malignancies, recent infections, or antibiotic use within the prior month. The study protocol was approved by the Ethics Committee and written informed consent was obtained from all participants.

Data Collection

Demographic data (age, sex) and clinical history (comorbidities, family history) were recorded using a standardized case record form. Laboratory assessments included FBS (enzymatic method), HbA1c (high-performance liquid chromatography), and spot ACR (immunoturbidimetry) to detect microalbuminuria, with values ≥30 mg/g indicating positivity [12]. Fundoscopy was performed by a trained ophthalmologist using a direct ophthalmoscope under mydriasis to assess retinopathy, graded as normal, mild NPDR, moderate NPDR, or not visualized due to technical or anatomical limitations (e.g., cataracts). Quality control measures, including duplicate testing and calibration, ensured consistency.

Statistical Analysis

Prevalence was calculated as the percentage of affected individuals within the cohort. Associations between variables (e.g., microalbuminuria and retinopathy) were evaluated using chi-square tests, with p-values <0.05 considered statistically significant. Age groups (30-39, 40-49, 50-59, 60-69, 70-79 years) and glycemic strata (FBS: 100-109, 110-119, 120-125 mg/dL; HbA1c: 5.6-6.0%, 6.1-6.5%) were analyzed for trends. Statistical analyses were conducted using SPSS version 20.0.

Demographic Profile

The study cohort had a mean age of 54.2 ± 12.3 years, with 63% of participants aged 50-69 years. The gender distribution was 58% males and 42% females, reflecting a community-based sample with 76% outpatients.

Prevalence of Microalbuminuria

Microalbuminuria was detected in 10 patients (10%), with a slightly higher prevalence among females (5/42, 12%) compared to males (5/58, 8.7%), though this was not statistically significant (p>0.05). Age-specific prevalence increased with advancing age: 8% (1/13) in the 30-39 group, 10% (2/20) in the 40-49 group, 12% (4/33) in the 50-59 group, 15% (2/13) in the 60-69 group, and 17% (1/6) in the 70-79 group. Glycemic analysis showed a prevalence of 7% (2/29) in the FBS range of 100-109 mg/dL, rising to 12% (5/45) in the 110-119 mg/dL range and 12% (3/26) in the 120-125 mg/dL range (p=0.04). For HbA1c, prevalence was 5% (3/59) in the 5.6-6.0% range and 17% (7/41) in the 6.1-6.5% range (p=0.03).

Table 1: MICROALBUMINURIA & HbA1C LEVELS

Prevalence of Retinopathy

Retinopathy was identified in 7 patients (7%), with 4 males (7%) and 3 females (7%) affected, showing no significant gender difference (p=0.045). Non-visualized retinopathy cases were noted in 10 patients (5 males, 9%; 5 females, 12%). Age-specific prevalence was 0% (0/13) in the 30-39 group, 5% (1/18) in the 40-49 group, 7% (2/29) in the 50-59 group, 9% (3/34) in the 60-69 group, and 17% (1/6) in the 70-79 group, with non-visualized cases rising to 33% (2/6) in the oldest group (p=0.02). FBS-related prevalence was 7% (2/29) in the 100-109 mg/dL range, 9% (4/45) in the 110-119 mg/dL range, and 4% (1/26) in the 120-125 mg/dL range, with non-visualized cases increasing to 15% (4/26) at the highest FBS level (p=0.03).

Table 2: RETINOPATHY AND LEVELS OF BLOOD SUGAR

Table 3: MICROALBUMINURIA AND RETINOPATHY CHANGES TABLE

Association between Microalbuminuria and Retinopathy

Among 83 patients with normal fundus findings, 96% (80/83) had no microalbuminuria, while 4% (3/83) did. In the 5 patients with mild NPDR, 60% (3/5) exhibited microalbuminuria, and in the 2 patients with moderate NPDR, 100% (2/2) had microalbuminuria. The association between fundus changes and microalbuminuria was statistically significant (p=0.0017), particularly when comparing normal fundus to mild NPDR groups.

study provides robust evidence that microvascular complications, namely microalbuminuria and retinopathy, are detectable in prediabetes, with prevalences of 10% and 7%, respectively. The slightly higher microalbuminuria prevalence in females (12% vs. 8.7% in males) aligns with observations by Haffner et al.[7], who noted gender-specific renal risk factors in prediabetic states, potentially linked to hormonal or anatomical differences. However, the lack of statistical significance (p>0.05) suggests that sample size or unmeasured confounders (e.g., obesity, dietary habits) may influence this trend, warranting further investigation[13].

The age-related increase in both conditions mirrors findings from Naranga et al.[14], who reported higher microalbuminuria prevalence in older prediabetic cohorts, attributed to cumulative glycemic exposure and declining renal reserve. The retinopathy prevalence escalating from 0% to 17% with age, alongside a 33% non-visualized rate in the 70-79 group, highlights diagnostic challenges in elderly populations, possibly due to cataracts or media opacities[15]. This is consistent with reports suggesting age-related ocular changes complicate retinopathy detection[16].

Glycemic control emerged as a critical determinant, with microalbuminuria prevalence increasing from 7% to 12% across FBS strata (p=0.04) and from 5% to 17% across HbA1c strata (p=0.03). This gradient supports the hypothesis that even modest hyperglycemia in prediabetes induces renal stress, aligning with Rothman et al.’s findings on early glucose transport defects[17]. The retinopathy prevalence, though lower, showed a similar trend, with non-visualized cases rising to 15% at higher FBS levels, suggesting subclinical changes that current diagnostics may miss, as noted by the ADA [18].

The significant association between microalbuminuria and retinopathy (p=0.0017) reinforces the concept of shared pathogenesis, likely involving endothelial dysfunction, oxidative stress, and advanced glycation end-products [19]. The 60% microalbuminuria rate in mild NPDR and 100% in moderate NPDR cases suggest a progression linked to glycemic damage, supporting the Mexico City Diabetes Study [7]. This correlation contrasts with Udit Narayan et al. [20] and Ramchandran Rajyalakshmi et al.[21], who reported lower retinopathy prevalence without gender differences, possibly due to regional or methodological variations (e.g., smaller sample sizes or different diagnostic tools).

Limitations include the modest sample size (100 patients) and single-center design, which may limit generalizability. The use of spot ACR, while convenient, may underestimate microalbuminuria compared to 24-hour urine collection, the gold standard [7]. Fundoscopy, though effective, faced challenges with non-visualized cases, potentially due to operator variability or patient factors (e.g., poor dilation). Future studies should incorporate larger, multicenter cohorts and advanced imaging (e.g., optical coherence tomography) to enhance diagnostic precision[22].

The implications are profound: early screening for microalbuminuria and retinopathy in prediabetes could guide preventive strategies, such as lifestyle modifications (e.g., diet, exercise) and glycemic control (e.g., metformin), potentially reducing T2DM incidence[23]. The gender and age trends suggest tailored approaches, while the association between complications highlights the need for integrated care addressing both renal and ocular health [24]. Public health policies should prioritize prediabetes screening, especially in high-risk populations like India.

This study demonstrates that microalbuminuria and retinopathy are prevalent in prediabetes, with a significant association (p=0.0017) that intensifies with disease progression. The findings advocate for proactive screening and management in prediabetic individuals to prevent the onset of T2DM and its microvascular complications. Larger-scale, multicenter research is essential to confirm these results, refine diagnostic criteria, and develop targeted interventions, ultimately improving patient outcomes in this high-risk population.

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