Management of prediabetes.
Prediabetes is an intermediate stage of hyperglycaemia, characterized by impaired fasting glucose, impaired glucose tolerance and/ or an HbA1c ranging from 5.7-6.4%. Prediabetes is associated with an increased risk of progression to overt diabetes and increased risk of cardiovascular disease. Several intervention studies have demonstrated that onset of diabetes can be prevented or delayed with intensive lifestyle modification and oral antidiabetic agents including metformin, thiazolidinediones and alpha-glucosidase inhibitors. Prediabetes management should focus on lifestyle modification and multiple risk factor management. In cases at high risk, use of oral antidiabetic agents may be considered.
Keywords: Prediabetes, Impaired fasting glucose, Impaired glucose tolerance, Diabetes prevention.
Prediabetes is recognized as an intermediate stage of hyperglycaemia, between normoglycaemia and overt diabetes mellitus. Guidelines differ slightly in their definition of prediabetes, as detailed in Table-1 and there has been debate over the lowering of fasting plasma glucose (FPG) cut-off from 110 mg/dl to 100 mg/dl and the inclusion of HbA1c as a diagnostic criterion, citing that this would result in a large number of individuals being diagnosed as prediabetic. Both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are characterized by varying degrees of insulin resistance and beta cell dysfunction.1 Patients with isolated IFG have predominant hepatic insulin resistance with increased hepatic glucose output and impaired first phase insulin secretion.
Patients with isolated IGT, on the other hand, have predominant skeletal muscle insulin resistance with reduced peripheral glucose utilization and impaired first and second phase insulin resistance. Over time, further decline in beta cell function may result in progression to overt diabetes.2 Prediabetes is associated with increased risk of macrovascular and microvascular complications, with IGT exhibiting a stronger association with cardiovascular risk.3
Table-1: Prediabetes - Diagnostic Cut-offs.
Parameter###Category###ADA Definition###WHO Definition
FPG###Impaired Fasting Glucose (IFG)###100-125 mg/dl###110-125 mg/dl
2hr OGTT###Impaired Glucose Tolerance (IGT)###140-199 mg/dl###140-199 mg/dl
Evaluation and Risk Assessment
While routine screening is not recommended, guidelines recommend a case-finding approach in individuals at risk of diabetes.4,5 IGT may be cumbersome to perform and instead, FPG and HbA1c can be assessed. However, there may be poor concordance between the FPG, 2hr OGTT (oral glucose tolerance test) value and HbA1c. Individuals who have combined IFG and IGT have higher risk of conversion to diabetes, especially if they have concurrent metabolic syndrome.2 The individual should be assessed for other risk factors for diabetes progression and cardiovascular disease, as enlisted in Table-2, rather than focusing on glucocentric numerical cut-offs.
Table-2: Risk factor assessment in patients with Prediabetes.
Overweight or obesity
Family history of diabetes
Family history of cardiovascular disease
History of gestational diabetes
Non-alcoholic fatty liver disease
Polycystic ovary syndrome
Prediabetes involves a long asymptomatic period of impaired glucose metabolism that can be diagnosed by measurement of FPG, 2hr OGTT value and/ or HbA1c. It offers an opportunity to delay or prevent further progression of dysglycaemia with lifestyle modification and pharmacological therapy. The ideal candidate for such intervention would be an individual who fulfills more than one prediabetes diagnostic criteria and is well motivated to initiate and maintain multifactorial strategies.6 Several prevention trials have demonstrated the utility of intensive lifestyle modification in preventing or delaying the progression to overt diabetes and in reducing other cardiovascular risk factors.78 Individuals should be encouraged to reduce 5-7% of body weight with restriction of calorie dense food and moderate intensity physical activity of 150 min per week or greater.6
Pharmacological agents like metformin, thiazolidinediones and alpha-glucosidase inhibitors have also demonstrated the potential to delay progression to diabetes and may be considered in those individuals with high risk of progression to diabetes and increased cardiovascular risk. Low dose metformin (250 mg twice daily) was as effective as lifestyle modification in the Indian Diabetes Prevention Program with a relative risk reduction of 26.4%.9 Metformin was associated with 18% reduced risk of progression to diabetes after 10 years in the DPP Outcomes study and was evaluated to be cost effective.10 The American Diabetes Association guidelines and American Association of Clinical Endocrinologist guidelines recommend use of pharmacological agents, especially metformin, in those individuals who fulfill multiple prediabetes diagnostic criteria and have additional risk factors.4,5
In Figure, we suggest an algorithm for management of patients with prediabetes. Weight loss therapies including bariatric surgery may be considered in those with morbid obesity.11 Treatment should focus on multifactorial risk factor management including smoking cessation, management of hypertension, dyslipidaemia, non-alcoholic fatty liver disease, polycystic ovary syndrome and cardiovascular disease.12
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2. Ferrannini E. Definition of intervention points in prediabetes. Lancet Diabetes Endocrinol 2014; 2:667-75. doi:10.1016/S2213-8587(13)70175-X.
3. Grundy SM. Pre-diabetes, metabolic syndrome and cardiovascular risk. J Am Coll Cardiol 2012; 59: 635-43.
4. American Diabetes Association, Standards of Care. Prevention or delay of type 2 diabetes. Diabetes Care 2017; 40(Suppl. 1):S44-S47 | DOI: 10.2337/dc17-S008.
5. Garber AJ, Abrahamson MJ, Barzilay JI, Lawrence B, Zachary T. Bloomgarden et.al. (2016) Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocrine Practice: 2016; 22: 84-113.
6. Kanat M, DeFronzo R, Abdul-Ghani MA. Treatment of prediabetes. World J Diabetes 2015; 6: 1207-1222.
7. Kerrison G, Gillis RB, Jiwani SI, Alzahrani Q, Kok S, Harding SE et.al. The effectiveness of lifestyle adaptation for the prevention of prediabetes in adults: a systematic review. Journal of Diabetes Research. 2017, DOI: 10.1155/2017/8493145
8. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403.
9. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V; Indian Diabetes Prevention Programme (IDPP). 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; 48:289-97. Epub 2006 Jan 4.
10. Aroda VR, Knowler WC, Crandall JP, Perreault L, Edelstein SL, Jeffries SL, et.al. Diabetes Prevention Program Research Group. Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/ Diabetes Prevention Program Outcomes Study. Diabetologia. 2017; doi: 10.1007/s00125-017-4361-9.
11. Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM et.al. and Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines (2016). American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocrine Practice: (Supplement 3) 2016; 22: 1-203.
12. Portero McLellan KC, Wyne K, Villagomez ET, Hsueh WA. Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus. Ther Clin Risk Manag 2014; 10: 173-88. doi:10.2147/TCRM.S39564.
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|Publication:||Journal of Pakistan Medical Association|
|Date:||Apr 30, 2018|
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