Data collected by the quality control system of the Belgian healthcare system enabled the study of a large, real-world population of well-characterised people living with type 1 diabetes. Over the last 20 years, we have observed an improvement in glycaemic control and LDL-cholesterol levels, but an increase in the prevalence of overweight, obesity and combined metabolic abnormalities in people living with type 1 diabetes.

In recent decades, the prevalence of obesity in the general population has increased, mainly due to the adoption of a progressively more sedentary lifestyle and the consumption of less healthy diets [21, 22]. In Belgium, age-adjusted obesity has increased from 11.5% in men and 11.1% in women in 1997 to 16.4% in men and 14.5% in women in 2018 [23]. In the current study, we show that the proportion of obesity in adults with type 1 diabetes in Belgium doubled from 12% in 2001 to 22% in 2022, confirming the finding that obesity is a growing emergency in people living with type 1 diabetes [4, 5, 22, 24,25,26].

The presence of a combination of metabolic abnormalities, such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as the metabolic syndrome or combined metabolic abnormalities, increases the risk of CVD in the general population as well as in people living with type 2 diabetes [9, 16, 27]. The prevalence of combined metabolic abnormalities ranges from 20–50% in the general adult population [6, 10, 28], but reaches almost 80% in people living with type 2 diabetes [6, 28]. An international review by Belete et al reported a pooled prevalence of combined metabolic abnormalities of 25.9% (95% CI 20.5, 31.6) in women and 22.5% (95% CI 16.7, 28.9) in men living with type 1 diabetes (studies performed between 2005 and 2020), with rates varying widely depending on patient characteristics and definition used [28]. Time-based subgroup analyses revealed a higher prevalence of combined metabolic abnormalities in the studies performed between 2015 and 2020 (26.6%) compared with those performed between 2005 and 2014 (21.8%) [28].

In the present study, we confirmed an increasing prevalence of combined metabolic abnormalities in adults living with type 1 diabetes, corrected for age and diabetes duration, irrespectively of the definition used. In 2001, combined metabolic abnormalities were identified in 27.5% of women and 31.7% of men, according to the WHO definition. In 2022, these proportions increased to 40.2% and 49.7% in women (p<0.01) and men (p<0.0001), respectively. The WHO definition of the metabolic syndrome/combined metabolic abnormalities includes microalbuminuria as a criterion, reflecting the pathophysiology of albuminuria seen in patients with type 2 diabetes, which may lead to a higher prevalence of combined metabolic abnormalities compared with other definitions. However, as albuminuria in people living with type 1 diabetes is typically a microvascular complication, indicating the early stages of renal disease, we repeated the analysis using the WHO definition of the metabolic syndrome/combined metabolic abnormalities without microalbuminuria. The increase in the prevalence of combined metabolic abnormalities remained when albuminuria was removed from the definition (from 21.8% in 2001 to 38.2% in 2022 in women [p<0.0001] and from 24.7% in 2001 to 46.4% in 2022 in men [p<0.0001]).

In our study, an increase in the prevalence of combined metabolic abnormalities was also observed when using the NCEP-ATPIII and IDF definitions of the metabolic syndrome/combined metabolic abnormalities, which use WC as the key obesity measure [28], but the overall prevalence was higher compared with the WHO definitions of the metabolic syndrome/combined metabolic abnormalities (with and without albuminuria). This may be due to the fact that WC data were only available from 2005 onwards and only for a minority of participants, although the small differences in threshold values for hypertension and HDL-cholesterol between definitions may also have had an effect. A recent Belgian study reported a prevalence of combined metabolic abnormalities in people living with type 1 diabetes of 30% according to the NCEP-ATPIII definition (data collected between 2018 and 2022) [29].

We have shown previously that, in people living with type 1 diabetes, glycaemic and lipid control improved over time due to a combination of provision of technology, education and quality monitoring [14]. HbA1c and LDL-cholesterol levels also decreased over time in the present study in people living with type 1 diabetes. Rates of lipid-lowering and antihypertensive therapy increased, which may be at least partially explained by the European Association for the Study of Diabetes and the American Diabetes Association consensus guidelines recommending more routinely cardiovascular treatment in addition to glucose-lowering treatment in people living with diabetes. As a result, the proportions of people being treated with lipid-lowering or antihypertensive drugs and thus by definition being identified as having dyslipidaemia or hypertension strongly increased, as did the number of people with combined metabolic abnormalities. However, disturbingly, obesity and central obesity became more prevalent with the decrease in HbA1c.

Those with combined metabolic abnormalities had higher glucose levels (HbA1c >58 mmol/mol or >7.5%) and (as per definition) more overweight and hypertension and worse lipid control compared to those without combined metabolic abnormalities. Our results are in line with the findings of Lee et al [10]. In their study, people with combined metabolic abnormalities had higher glucose levels (HbA1c of 68 mmol [8.4%] vs 64 mmol [8.0%]) and a significantly higher prevalence of hypertension (89% vs 29%), dyslipidaemia (combined elevated TG levels and lower HDL-cholesterol levels, 50% vs 9.1%) and obesity (50% vs 7.2%) compared to those without combined metabolic abnormalities. In our population, despite higher use of statins and antihypertensive drugs in those with combined metabolic abnormalities, approximately one-fifth of individuals with combined metabolic abnormalities were not on statins. In addition, one-fifth of those with combined metabolic abnormalities smoked, further accelerating the risk of micro- and macrovascular complications in this population.

We found a strong relationship between combined metabolic abnormalities and the prevalence of CVD, but also eye complications, peripheral neuropathy and chronic kidney disease, corrected for age, diabetes duration and HbA1c. This finding is in line with some previous observations, depending on the definition of the metabolic syndrome/combined metabolic abnormalities used, and highlights the importance of identification of combined metabolic abnormalities and initiation of more aggressive therapeutic approaches in these patients [10, 12, 22, 30].

Our data show that people with combined metabolic abnormalities are less often treated with CSII. The maximum insulin storage capacity of insulin pumps may have influenced treatment decisions for individuals with combined metabolic abnormalities, especially those with higher body weight. However, no patch pumps for which the maximum insulin storage capacity could be a major issue were available in Belgium over the time period of data collection.

In our population, people with combined metabolic abnormalities are more often treated with adjunct therapies such as metformin, SGLT2 inhibitors and GLP1 receptor agonists. Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant conditions. It decreases hepatic glucose production and enhances insulin-stimulated glucose disposal in peripheral tissues [22, 31]. Metformin is an inexpensive and well-established oral glucose-lowering drug, and the first-line treatment in patients with type 2 diabetes. It is frequently used as an adjunct to intensive insulin therapy in people living with type 1 diabetes [32, 33]. It has been shown to have some benefit in reducing insulin doses and weight, although no long-term beneficial effects were observed when patients were followed for 10 years [34]. The recent international study ‘REducing with Metformin Vascular Adverse Lesions’ (REMOVAL) suggests a reduction in cardiovascular risk as a result of metformin use in people with long-standing type 1 diabetes [35]. However, in most countries, including Belgium, there is no official indication for use of metformin in patients with type 1 diabetes. Nevertheless, 11% of our type 1 diabetes population used metformin as an adjunct therapy (2022 data), in line with 8–15% of the population reported in Scotland (2016 data) [35] and 4–7% of the population in the USA (T1D Exchange Registry, 2016–2018 data) [26].

As SGLT2 inhibitors and GLP1 receptor agonists are intended for use in people living with type 2 diabetes, use of these drugs for treatment of people living with type 1 diabetes is rare and they are prescribed on an individual basis. SGLT2 inhibitors reduce blood glucose levels by decreasing the resorption of glucose in the kidneys, and exert nephroprotective and cardioprotective effects [22]. Studies of the use of SGLT2 inhibitors in people living with type 1 diabetes have shown a positive effect on BMI and daily insulin dose, but warn of a potential increased risk of euglycaemic ketoacidosis [4, 36]. While further research is needed on the potential cardiorenal benefits of use of SGLT2 inhibitors in people with type 1 diabetes, for the moment it may be advisable to prescribe them only to compliant patients with a BMI greater than 27 kg/m2, and to interrupt their use in cases of insulin dose reduction and dehydration [37, 38]. GLP1 receptor agonists enhance insulin secretion in a glucose-dependent manner, inhibit the release of glucagon, promote satiety and slow down gastric emptying. In addition to their glucose-lowering effect, GLP1 receptor agonists have a positive effect on BMI and cardiovascular events [4, 22, 39]. Due to their safety profile and demonstrated positive effect on obesity and insulin resistance in people living with type 1 diabetes, these drugs may be used as an adjunct therapy in such patients [39].

Despite important strengths, such as the size and quality of the database as well as the duration of observation, our study has limitations. The cross-sectional nature of the data does not allow individual longitudinal follow-up or investigation of causality. Also, the lack of information on physical activity, ethnicity or socioeconomic status is a weakness.

People living with type 1 diabetes are increasingly affected by overweight, obesity and combined metabolic abnormalities. This co-occurrence of diseases may result in a further elevated risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive drugs and statins. The use of adjunct therapies deserve to be explored more thoroughly in this population as a tool to reduce the risk of complications.