Addressing the Continuum of Dysglycaemia and Vascular Complications in Prediabetes and Type 2 Diabetes: Need for Early and Intensive Treatment

Figures & data

Table 1 Diagnosis of Prediabetes and Type 2 Diabetes

	Type of Measurement
	Fasting Plasma Glucose	Post-OGTT Glucose^a	HbA1c	Random Glucose
Prediabetes:
Impaired fasting glucose:	5.7–6.9 mmol/L(100–125 mg/dL)^b	–	–	–
Impaired glucose tolerance:		7.8–11.0 mmol/L (140–199 mg/dL)	–	–
Elevated HbA1c	–	–	5.7–6.4% (39–47 mmol/mol)^c	–
Type 2 diabetes:	≥7.0 mmol/L (≥126 mg/dL)	≥11.1 mmol/L (≥200 mg/dL)	≥6.5% (≥47 mmol/mol)	≥11.1 mmol/L (≥200 mg/dL)

Notes: ^aGlucose values following a standard, 75 g oral glucose tolerance test; ^blower cut-off value = 6.1 mmol/L (110 mg/dL) according to World Health Organization criteria; ^cor increase in HbA1c of ≥10% according to American Diabetes Association criteria. Data from these studies.^10,11

Abbreviation: OGTT, oral glucose tolerance test.

Figure 1 Associations between different definitions of prediabetic states and adverse macrovascular outcomes from a systematic review.

Notes: Definitions of prediabetic states shown here were according to American Diabetes Association criteria. Data from Gujral et al.³⁰

Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; IFG, impaired fasting glucose; IGT, impaired glucose tolerance.

Figure 2 Schematic representation of key goals in managing the diabetes continuum.

Notes: ^aUse with caution in combination with SGLT2 inhibitor or sulfonylurea to minimise risk of hypoglycaemia; ^bpatients with established cardiovascular disease or heart failure at presentation (see text); ^cfor selected people with prediabetes (see text⁹⁴) and/or at diagnosis of type 2 diabetes consistent with joint guidance from the American Diabetes Association/European Association for the study of Diabetes.⁴

Abbreviation: AD, antidiabetic drug.

Table 2 European and US Guidance on the Use of Metformin to Prevent or Delay the Onset of Type 2 Diabetes

	Overview of Recommendations on Pharmacologic Diabetes Prevention
ADA (2023)^Citation94	Consider adding metformin to lifestyle intervention especially for subjects with:  ● BMI ≥35 kg/m^2,  ● Age 25–59 years  ● Fasting glucose >6.1 mmol/L (110 mg/dL)  ● HbA1c >6.0%  ● Prior history of gestational diabetes
NICE (2020)^Citation96	Consider metformin (+ lifestyle intervention) for people whose HbA1c is rising despite lifestyle intervention, or where the patient is unable to undertake a lifestyle intervention – especially if BMI is ≥35 kg/m^2 Discontinue after 6–12 months if there is no improvement in glycaemia Also consider orlistat for weight loss if BMI ≥28 kg/m^2
European expert group (2010)^Citation95	Consider metformin or acarbose for diabetes prevention in people with IGT Consider orlistat for obese subjects
ESC (2019)^Citation101	Consider lifestyle changes to reduce the risk of new-onset diabetes and cardiovascular risk only, with no advice on pharmacological intervention in people with prediabetes

Note: All recommendations on metformin assume an absence of contraindications and concurrent application of a lifestyle intervention.

Abbreviations: ADA, American Diabetes Association; EASD, European Society for the Study of Diabetes; ESC, European Society of Cardiology; NICE, National Institute of Health and Care Excellence.

Figure 3 Principal sources of therapeutic inertia: contributions from the healthcare system, healthcare providers, and the patients themselves.

Notes: Data from Khunti S, Khunti K, Seidu S.¹⁰⁵ Percentages shown are the relative contributions of each domain to the overall problem of clinical inertia in the opinion of the authors of reference.¹⁰⁵

Draznin B; American Diabetes Association Professional Practice Committee; American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl1):S17–S38. doi:10.2337/dc22-S002

 PubMedGoogle Scholar

World Health Organization, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF consultation. Available from: www.who.int/diabetes/publications/Definitionanddiagnosisofdiabetes_new.pdf. Accessed December 30, 2022.

 Google Scholar

Gujral UP, Jagannathan R, He S, et al. Association between varying cut–points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta–analysis. BMJ Open Diabetes Res Care. 2021;9:e001776. doi:10.1136/bmjdrc-2020-001776

 PubMed Web of Science ®Google Scholar

ElSayed NA, Aleppo G, Aroda VR, et al. 3. Prevention or delay of type 2 diabetes and associated comorbidities: standards of care in diabetes-2023. Diabetes Care. 2023;46(Supplement_1):S41–S48. doi:10.2337/dc23-S003

 PubMedGoogle Scholar

Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65:1925–1966. doi:10.1007/s00125-022-05787-2

 PubMed Web of Science ®Google Scholar

National Institute for Health and Care Excellence. Group and individual–level interventions to prevent type 2 diabetes among people at high risk. Available from: https://www.nice.org.uk/guidance/PH38/chapter/Recommendations#metformin. Accessed December 30, 2022.

 Google Scholar

Paulweber B, Valensi P, Lindström J, et al. A European evidence–based guideline for the prevention of type 2 diabetes. Horm Metab Res. 2010;42(Suppl 1):S3–S36. doi:10.1055/s-0029-1240928

 PubMed Web of Science ®Google Scholar

Petrie JR, Rossing PR, Campbell IW. Metformin and cardiorenal outcomes in diabetes: a reappraisal. Diabetes Obes Metab. 2020;22:904–915. doi:10.1111/dom.13984

 PubMed Web of Science ®Google Scholar

Khunti S, Khunti K, Seidu S. Therapeutic inertia in type 2 diabetes: prevalence, causes, consequences and methods to overcome inertia. Ther Adv Endocrinol Metab. 2019;10:2042018819844694. doi:10.1177/2042018819844694

 Web of Science ®Google Scholar