EXPERT INSIGHT

Managing the early-onset type 2 diabetes mellitus: Target the major hurdles

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Dr. Luk, On-Yan Andrea

Associate Professor,
Department of Medicine & Therapeutics,
The Chinese University of Hong Kong

​People with young-onset diabetes have a worse metabolic risk profile compared to those with late-onset disease. This group has higher risks for cardiovascular and kidney complications at any given age, driven by the longer disease duration.1 In Hong Kong, while the mortality rate decrease in people with late-onset diabetes, it has not changed significantly in those with young-onset diabetes. In a recent interview with Omnihealth Practice, Dr Luk, On-Yan Andrea discussed the latest trends and effective management of early-onset type 2 diabetes in Hong Kong.

The burden of early-onset type 2 diabetes and risk indicators

Diabetes is a chronic disease characterized by its silent and progressive nature, and contributes to significant morbidities and premature mortality in those affected.The prevalence of type 2 diabetes increases with age, however, currently there is an alarming trend of an increasing number of younger people being diagnosed with diabetes globally.2 In Hong Kong, the incidence rate of type 2 diabetes has stabilized among older people but continued to increase in those between the ages of 20-39 years.4 Compared to their counterparts with late onset of diabetes, these young individuals face long duration of the disease leading to an increased lifetime risk of diabetes-related complications.2 Besides, there is marked aetiologic and phenotypic heterogeneity which can affect responses to different treatment to give rise to variable clinical outcomes.2 Risk factors for young-onset diabetes include family history of diabetes especially diabetes affecting young family members, phenotypes of insulin resistance (central obesity, raised triglyceride levels, low high-density lipoprotein cholesterol levels, high blood pressures, fatty liver disease), history of gestational diabetes or polycystic ovarian syndrome in women, history of androgen deficiency in men, and known impaired glucose tolerance and/or impaired fasting glucose.2

In Hong Kong, the prevalence of diabetes is around 10%, and among them only 60% are diagnosed. Among people with known diabetes, up to one in five have diabetes with onset below the arbitrary age of 40 years.1,5,6 The key modifiable risk factors for young-onset diabetes include adoption of a healthy diet, regular physical exercise and smoking cessation. In a Chinese population, it was found that there was a 6-7 fold increase of risk for an individual to develop diabetes in the presence of a family history of young-onset diabetes, independent of other risk variables.3 Incidence rates of diabetes-related complications and mortality have declined substantially in people with diabetes, except in young people aged 20–44 years, who have a 4-9 fold higher rate of death relative to their counterparts without diabetes.4,5 The less marked improvements in morbidities and mortality among young people in Hong Kong and in other regions are of concern due to these individuals being at the prime age of economic productivity, with major adverse impact at both a personal and society level.6

Severe manifestations of the disease at relatively younger age

Delayed identification of the disease and poor clinical immersion of the affected individuals are identified as the main causes of severe disease manifestations of diabetes in younger people. According to a 7-year prospective cohort study of 9,509 people with type 2 diabetes from the Hong Kong Diabetes Registry and a cross-sectional study of 15,341 people with type 2 diabetes from the Joint Asia Diabetes Evaluation program, those with early-onset diabetes were less likely to achieve treatment goals.1,5 Importantly, their risks of cardiovascular and kidney diseases were increased by 40%-50% compared with older aged people at any given age.1 It was recently estimated that a young person with diabetes spends on average 100 days in hospital by the age of 75 years (Figure 1).7 This high cumulative bed days can be effectively lowered with improved control of blood glucose and other risk factors.  

 

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Overweight is an important risk multiplier in young people with diabetes. In a study of 2,323 people with young-onset diabetes, the overweight group had the highest incidences of both cardiovascular events and end-stage kidney disease, followed by normal-weight people with type 2 diabetes and those with type 1 diabetes.8 The increased risk ratio of cardiovascular and kidney events for the young-onset diabetes was driven primarily by obesity and accompanying hypertension and dyslipidaemia.8 These findings highlight the impact of young-onset diabetes on the development of chronic complications and underscore the need for more effective interventions including global risk factor management in this young group.8 Furthermore, it draws attention to the existing shortfalls in identifying high-risk individuals and the challenges in managing this demanding cohort of patients.8

Personalized glycemic targets are essential in dealing with the early-onset type 2 diabetes

Current management guidelines are mostly based on the clinical trial data of older population, as there is less solid evidence for treatment effects in younger people. The recommended management of young-onset diabetes is not well differentiated from that for older people. However, more stringent blood glucose control should be recommended for young-onset diabetes in order to lower the lifelong glycemic burden in this group. According to the guidelines of the American Diabetes Association (ADA), a HbA1c level of 7.0% is recommended for most people with diabetes. However, for younger individuals, the HbA1c level should be tightened to around 6.0%-6.5%. In addition, the ADA suggests an individualization of glycemic targets according to individual risk indicators (Figure 2).9

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In a large prospective cohort of Chinese with type 2 diabetes, the variability of HbA1c was an independent predictor of cardiovascular and kidney complications.10 Due to these potential hazards of excessive glycemic fluctuation on the clinical outcomes, periodic monitoring and stringent blood glucose maintenance are essential.10 Since younger people can tolerate most pharmacological therapies better than older individuals, newer pharmacological agents like sodium-glucose co-transporter-2  inhibitors and glucagon-like peptide-1 receptor agonists could be utilized in stabilizing the HbA1c levels. In addition, younger people should be continuously motivated to adopt and maintain healthy lifestyle choices. Family and peer support are effective in fulfilling these objectives.

Can we prevent the complications of early-onset type 2 diabetes

Population awareness is one of the key factors in early identification of young-onset diabetes as young people are less likely to be screened. Young people should be educated on potential risk factors and encouraged to get screened before full-blown disease has evolved. As mentioned, there are many risk factors which frequently cluster to amplify the risk of developing diabetes. An individual with multiple risk factors should receive regular surveillance and clinical assessment to detect “prediabetes” or diabetes to enable early intervention.2 Similar to diabetes management, screening and treatment of high-risk individuals should be personalized and be implemented as soon as possible.2 Regular screening, lifestyle modifications and behavioral changes remain the cornerstones for the prevention of diabetes, although some evidence also exists for early pharmacological intervention.

Specific unmet needs of the early-onset DM

There is now increasing evidence highlighting the poor adherence to treatment and medical follow-up, and high levels of psychosocial stress in young people with diabetes.7 Additionally, the aetiologic and phenotypic heterogeneity as well as the lack of management guidance also contribute to the suboptimal control in this group.6 In this connection, around 8% of people with young-onset diabetes previously labelled as type 2 diabetes have latent autoimmune diabetes based on the presence of anti-glutamate decarboxylase antibodies, and 3%-4% have monogenic diabetes.11 Delineation of the type of diabetes requires careful consideration of a person’s clinical presentation, past responses to pharmacotherapy, and family history of diabetes and other diseases, in addition to appropriate investigations such as measurement of anti-islet cell antibodies, C-peptide level and genetic tests for monogenic diabetes. Accurate identification of diabetes type has clear clinical implication on treatment, prognostication, and screening of family members, as appropriate.

There is evidence of co-existing psychiatric condition and diabetes especially in young people. Young people with diabetes generally have more negative emotions than older ones as they are less prepared for receiving a diagnosis of a chronic disease and experience more difficulties coping with diabetes self-management in the face of other life priorities. Depression in people with diabetes is associated with both hyperglycemia and hypoglycemia accompanied by inadequate self‐care and treatment adherence.12 The co-occurrence of diabetes and depression or other psychiatric conditions can lead to worse health outcomes. In this light, physicians should consider underlying depression or emotional distress and should adopt more holistic approach to manage these individuals.12 Greater engagement with family and peer groups and choosing effective cognitive-behavioral therapy could enhance the overall outcome in people with young-onset diabetes.

Message to the physicians and conclusion

Stringent blood glucose and global risk factor control are essential to prevent development of diabetes-related complications in people with young-onset diabetes. If possible, a tight glycemic target of HbA1c levels of 6.0%-6.5% should be achieved in these individuals. Young people with diabetes should be appropriately educated about their inherent high lifetime risk of complications and the narrow window of opportunity to positively alter their prognosis if disease control can be adequately achieved early on in their diabetes trajectory. There is a strong call for increased awareness of young-onset diabetes in the community, and opportunistic screening for diabetes should be undertaken in people with risk factors for early detection and treatment.


References
  1. Chan JCN et al. Premature mortality and comorbidities in young-onset diabetes: a 7-year prospective analysis. Am J Med. 2014;127(7):616-624.
  2. Kong APS et al. Detecting people at high risk of type 2 diabetes- How do we find them and who should be treated? Best Pract Res Clin Endocrinol Metab. 2016;30(3):345-355.
  3. Zhang Y et al. High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis. Diabet Med. 2017;34(12):1701-1709.
  4. Wu H et al. Secular trends in all-cause and cause-specific mortality rates in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study. Diabetologia. 2020;63(4):757-766.
  5. Wu H et al. Trends in diabetes-related complications in Hong Kong, 2001-2016: a retrospective cohort study. Cardiovasc Diabetol. 2020;19(1):60.
  6. Luk AOY et al. Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: A retrospective cohort study. PLoS Med. 2020;17(2):e1003052.
  7. Ke C et al. Excess Burden of Mental Illness and Hospitalization in Young-Onset Type 2 Diabetes: A Population-Based Cohort Study. Ann Intern Med. 2019;170(3):145-154.
  8. Luk AOY et al. Prospective study on the incidences of cardiovascular-renal complications in Chinese patients with young-onset type 1 and type 2 diabetes. Diabetes Care. 2014;37(1):149-157.
  9. Association AD. Standards of Medical Care in Diabetes—2019 Abridged for Primary Care Providers. Clinical Diabetes. 2019;37(1):11-34.
  10. Luk AOY et al. Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry. Diabetes Metab Res Rev. 2013;29(5):384-390.
  11. Luk AOY et al. Diabetes-Related Complications and Mortality in Patients With Young-Onset Latent Autoimmune Diabetes: A 14-Year Analysis of the Prospective Hong Kong Diabetes Register. Diabetes Care. 2019;42(6):1042-1050.
  12. Zhang Y et al. Depression in Chinese patients with type 2 diabetes: associations with hyperglycemia, hypoglycemia, and poor treatment adherence. J Diabetes. 2015;7(6):800-808.
ADA
HbA1c
EARLY-ONSET
TYPE 2 DIABETES MELLITUS
T2DM
AMERICAN DIABETES ASSOCIATION