We spoke with Naveed Sattar, MD, PhD with the University of Glasgow, Scotland about the Credence Study and its implications for T2D care.  Dr. Sattar is the co-lead author of an article published in Circulation based on analysis of Swedish National Diabetes Registry data which showed that diabetes complications and early death are disproportionately associated with early in life T2D diagnosis.

Age of Diagnosis Impact

“Those diagnosed with T2DM at 45 years of age lose roughly 6 years of life compared with healthy men and women the same age, said Naveed Sattar. “The younger a patient is when diagnosed with type 2 diabetes, the worse their cardiovascular disease prognosis and the shorter their lifespan.”

“Our paper adds more fuel to the idea that being diagnosed with type 2 diabetes in your 20s, 30s, or even 40s is associated with considerably more harm as it relates to the excess risk of complications.

“There are considerably more life-years lost. When you’re around 20 years old and diagnosed with type 2 diabetes, you will lose more than a decade of life expectancy, which is on par with type 1 diabetes. Whereas if you develop type 2 diabetes at the other end of the age spectrum, 80 years old, you don’t lose any life expectancy.

“The bottom line, said Sattar, is that type 2 diabetes is a completely different disease in terms of toxicity in the very young and old.

Specific Findings

Individuals without cardiovascular disease diagnosed with type 2 diabetes at 40 years or younger had the highest risk of cardiovascular morbidity and mortality when compared with controls. The hazard ratios for various clinical outcomes in this young population were as follows:

• HR 2.05 (95% CI 1.81-2.33) for total mortality
• HR 2.72 (95% CI 2.13-3.48) for cardiovascular mortality
• HR 1.95 (95% CI 1.68-2.25) for noncardiovascular mortality
• HR 4.33 (95% CI 3.82-4.91) for coronary heart disease
• HR 3.41 (95% CI 2.88-4.04) for acute MI
• HR 4.77 (95% CI 3.86-5.89) for heart failure

The risk of stroke was more than threefold higher in men and women 40 years and younger diagnosed with type 2 diabetes, while the risk of atrial fibrillation was twofold higher.

Estimating the impact of diabetes on longevity, the researchers determined that a diagnosis of type 2 diabetes at roughly 15 years of age led to a loss of approximately 12 years of life. Diagnosis at 45 years lessened the lifespan by roughly 6 years, while a diagnosis at 65 years shaved off 2 years of life. At 80 years, a diagnosis of type 2 diabetes had no measurable effect on life-years lost.  

Aggressive Treatment Earlier  

The results, according to Sattar, should stimulate guideline committees to consider being more prescriptive with medical therapy in this younger T2D population.

“While we have hesitated in giving younger people drugs, such as statins and blood pressure-lowering medications, we also know it’s harder to control blood sugar levels when they develop diabetes younger because it progresses much faster.

“While lifestyle modification remains the cornerstone of cardiovascular risk prevention, physical activity is much harder for these heavier, younger patients, and major weight loss in the range of 20-30 kilograms is very difficult.   

“In contrast, aggressive T2D drug interventions in younger people make more sense and the news from Credence is important.  It is already best practice to use SGLT2 inhibitors for T2D treatment in those with prior heart disease or stroke and its added benefits in reducing kidney disease and other complications make it even more attractive. We need trials of these agents in younger people with T2 diabetes.

More focus on newer drugs and weight reduction in younger T2D?

Doctors now have at their disposal newer diabetes drugs that not only improve sugar levels but also aid weight loss. Other than the SGLT2 inhibitors, which work to remove excess sugar by excreting it in the urine, we have other classes such as the GLP-1 receptor agonists which lessen appetite, and so weight.

These drugs have also been shown to lower risk of heart attacks and stroke.  It may be combinations of these two newer diabetes drug classes will reap far better outcomes in younger people with T2D than the normal approach of progressing from metformin to sulfonylureas or insulin.

Given our findings of higher risks in younger-onset T2D, we urgently need trials to test these newer drugs in younger patients.

Sources

• Sattar N, Rawshani A, Franzén S, et al. Age at diagnosis of type 2 diabetes mellitus and associations with cardiovascular and mortality risks: findings from the Swedish National Diabetes Registry. Circulation2019; Epub ahead of print.
• Perkovic V, Jardine B, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy [published online April 14, 2019]. N Engl J Med. doi: 10.1056/NEJMoa1811744.
• Steinarsson AO, Rawshani A, Gudbjörnsdottir S, Franzén S, Svensson AM, Sattar N. Short-term progression of cardiometabolic risk factors in relation to age at type 2 diabetes diagnosis: a longitudinal observational study of 100,606 individuals from the Swedish National Diabetes Register. Diabetologia. 2018 Mar;61(3):599-606. doi: 10.1007/s00125-017-4532-8. Epub 2018 Jan 9. PubMed PMID: 29318343.
• Rawshani A, Sattar N, Franzén S, Rawshani A, Hattersley AT, Svensson AM, Eliasson B, Gudbjörnsdottir S. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet. 2018 Aug 11;392(10146):477-486. doi: 10.1016/S0140-6736(18)31506-X. Epub 2018 Aug 9. PubMed PMID: 30129464.
• Sattar N. Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future. BMC Med. 2019 Feb 26;17(1):46. doi: 10.1186/s12916-019-1281-1. PubMed PMID: 30803451; PubMed Central PMCID: PMC6390346.