Early intervention in prediabetes is crucial to prevent progression to diabetes

Dr Abdul Hamid Zargar, Endocrinologist, Centre for Diabetes and Endocrine Care, Srinagar, Jammu & Kashmir

Noncommunicable diseases (NCDs) including heart disease, cancer, chronic respiratory diseases and diabetes are a major health burden in India. With a prevalence of 15.3%, prediabetes, the precursor to type 2 diabetes, also adds significantly to this burden.¹ In a 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES), about 45% of individuals with normoglycemia converted to dysglycemia; 25.7% developed prediabetes and 19.4% developed diabetes.² 

Effective strategies for the primary prevention of diabetes are therefore needed in India, more so because of the distinct characteristics of the Asian Indian phenotype, which includes a low body mass index (BMI), high insulin resistance, early onset of diabetes and lower thresholds for diabetes risk factors.³ There is now compelling epidemiological evidence to show that Asian Indians with prediabetes develop type 2 diabetes more quickly compared to other ethnic populations.⁴

The transition from prediabetes to diabetes provides a critical window of opportunity for intervention. Timely action can reduce the incidence of complications associated with prediabetes with improved outcomes for patients and also eases the burden on the healthcare system.⁵

Prediabetes: A risk factor for vascular complications

“Prediabetes is an incremental risk factor for adverse cardiac events”.⁶ It is associated with higher odds of adverse cardiovascular events such as acute coronary syndrome (ACS), acute ischemic stroke and acute heart failure.⁶ An umbrella review of 95 meta-analyses of prospective studies found that prediabetes was associated with increased risk for all-cause mortality, coronary heart disease, stroke, heart failure, atrial fibrillation and chronic kidney disease, with risk ranging from 6% to 101%. The risk of cancer and all-cause dementia was also increased. ⁷

Early intervention with antidiabetic medications, intensive lifestyle modification, or both may be able to delay or stop the progression of prediabetes to type 2 diabetes and associated complications,⁸  both micro- and macrovascular.

Screening for prediabetes

The American Diabetes Association (ADA) has defined prediabetes as HbA1c of 5.7–6.4% or fasting plasma glucose between 100 and 125 mg/dL (impaired fasting glucose) or 2-hour plasma glucose between 140 and 199 mg/dL during 75-g oral glucose tolerance test (OGTT) (impaired glucose tolerance).  According to ADA 2024, persons of any age who are overweight or obese and who have ≥risk factors should be tested for prediabetes or type 2 diabetes, using fasting plasma glucose, 2-hour plasma glucose during 75-g OGTT and HbA1c, even in the absence of symptoms. Screening should start at age 35 for everyone else. If the results are normal, then testing should be repeated every three years.⁹

In its latest position statement, the International Diabetes Federation (IDF) states that the 1-hour post-load plasma glucose ≥ 155 mg/dL in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to type 2 diabetes including micro- and macrovascular complications. It recommends lifestyle intervention and referral to a diabetes prevention program for individuals with a 1-h plasma glucose of 155 mg/dL or more. ¹⁰

The Madras Diabetes Research Foundation-Indian Diabetes Risk Score (MDRF-IDRS) was developed as a screening tool for diabetes and prediabetes among Indians using four variables: age, waist circumference, regular exercise and family history. Based on the score (out of a total score of 100), persons were categorized as low-risk (score <30), moderate-risk (score 30–50) or high-risk (score ≥60). Its validity as a cost-effective tool for primary mass screening of diabetes has been established. ¹¹ With an area under the curve (AUC) of 0.83, the IDRS shows good accuracy in detecting people with diabetes and those at risk of developing diabetes. ¹²

Early intervention in prediabetes is crucial to prevent progression to diabetes

An analysis of the Diabetes Prevention Program (DPP) trial found that the incidence of diabetes, using HbA1c ≥6.5% as the criterion, decreased by 44% with metformin and 49% with lifestyle change during the DPP. But after a decade of follow-up, the reduction in the incidence of diabetes was 38% with metformin and 29% with lifestyle interventions. Unlike the DPP and the DPPOS, which primarily assessed diabetes prevention based on glucose criteria and showed superiority of lifestyle modifications, this analysis showed that both metformin and lifestyle interventions had comparable effectiveness in preventing diabetes when defined by HbA1c criteria. ¹³

Metformin in diabetes prevention

Metformin is the only drug to be used for the prevention or delaying of type 2 diabetes. It is especially indicated in persons with prediabetes, especially those who are aged 60 years and older, have a BMI >35 kg/m2, women with a history of gestational diabetes and in whom lifestyle changes alone are not enough to improve glucose tolerance and reduce body weight. ⁴

The effectiveness of metformin in preventing diabetes in Indian patients has been established in a systematic review and meta-analysis of 17 trials involving 30,474 participants. Use of metformin was associated with 35% reduction in the probability of progressing from prediabetes to type 2 diabetes with pooled odds ratio (OR) of 0.65 versus the control group. Metformin also lowered the odds of developing type 2 diabetes by 42% with pooled risk ratio of 0.58. These findings highlight the potential of metformin as an effective intervention for diabetes prevention, particularly in high-risk populations.¹⁴

The ICMR (2018) guidelines for management of type 2 diabetes also recommend use of metformin as adjunct to lifestyle measures for those who are likely to progress rapidly to diabetes from the prediabetes stage. ¹⁵

Conclusion

Prediabetes is fast becoming a major public health concern, which contributes significantly to the disease burden, both globally and in India. The consequences of prediabetes extend beyond the risk of developing type 2 diabetes and also include various metabolic and vascular complications including cardiovascular diseases. These chronic health issues result in substantial healthcare expenses. This scenario underscores the importance of early identification and management of prediabetes through lifestyle changes and, if required, the use of medications such as metformin.

With 74 million people with diabetes, India is only next to China (140 million) and this number is projected to increase to 124 million by 2045.¹⁶

An Expert Group Consensus Statement on prediabetes in India aptly states, “Prediabetes, however, should not be considered a path to diabetes rather it should be a window of opportunity for the prevention of diabetes…early screening, detection, and treatment of prediabetes should be made a national priority”. ⁴

References

1. Anjana RM, et al; ICMR-INDIAB Collaborative Study Group. Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17). Lancet Diabetes Endocrinol. 2023;11(7):474-89.
2. Anjana RM, et al. Incidence of diabetes and prediabetes and predictors of progression among Asian Indians: 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES). Diabetes Care. 2015;38(8):1441-8.
3. Ramachandran A, et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006;49(2):289-97.
4. Das AK, et al. An Expert Group Consensus Statement on “Approach and Management of Prediabetes in India”. J Assoc Physicians India. 2022;70(12):69–78.
5. Chawla R. Don’t let the “Pre” of Prediabetes fool you!. Int J Diabetes Dev Ctries. 2023;43:845-6.
6. Nanavaty D, et al. Prediabetes is an incremental risk factor for adverse cardiac events: A nationwide analysis. Atheroscler Plus. 2023:54:22-26.
7. Schlesinger S, et al. Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies. Diabetologia. 2022;65(2):275-85.
8. Gottwald-Hostalek U, et al. Vascular complications in prediabetes and type 2 diabetes: a continuous process arising from a common pathology. Curr Med Res Opin. 2022;38(11):1841-51.
9. American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S20-S42.
10. Bergman M, et al. International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes. Diabetes Res Clin Pract. 2024;210:111636.
11. Khan MM, et al. Validity of Indian Diabetes Risk Score and its association with body mass index and glycosylated hemoglobin for screening of diabetes in and around areas of Lucknow. J Family Med Prim Care. 2017;6(2):366-73.
12. Sengupta B, et al. Validation of Indian Diabetes Risk Score for screening prediabetes in West Tripura district of India. Indian J Community Med. 2021;46(1):30-4.
13. Diabetes Prevention Program Research Group. HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: a randomized clinical trial. Diabetes Care. 2015;38(1):51-8.
14. Patel D, et al. The effectiveness of metformin in diabetes prevention: a systematic review and meta-analysis. Cureus. 2023;15(9):e46108.
15. ICMR guidelines for management of type 2 diabetes 2018. Available at: https://main.icmr.nic.in/sites/default/files/guidelines/ICMR_GuidelinesType2diabetes2018_0.pdf. Accessed on August 8, 2024.
16. IDF Diabetes Atlas 10th edition. 2021. Available at: https://diabetesatlas.org/atlas/tenth-edition/. Accessed on August 8, 2024.