COMBINSI (COMBat to INSufficient Insulin therapy) - A Portuguese project in type 2 diabetes.

BACKGROUND: Inadequate glycemic control in type 2 diabetes (T2D) increases the risk of diabetes-related complications. Insulin initiation is often delayed for several years. This study aims to estimate the adequacy of insulin therapy prescription to people living with T2D in a primary care setting. MATERIAL AND METHODS: This was a cross-sectional study based on adults with T2D in a Portuguese local health unit between January 2019 and January 2020. Subjects under insulin therapy were compared with non-insulin-treated subjects with Hemoglobin A1c (HbA1c) ≥9% regarding clinical and demographic characteristics. The proportion of insulin-treated subjects in both of these groups was defined as insulin therapy index. RESULTS: Our study included 13,869 adults living with T2D, among whom 11.5% were treated with insulin therapy and 4.1% had HbA1c ≥ 9% and were not under insulin therapy. Insulin therapy index was 73.9%. When comparing with non-insulin-treated subjects with HbA1c ≥ 9%, insulin-treated subjects were significantly older (75.8 vs 66.2 years p < 0.001), had lower HbA1c (8.3 vs 10.3% p < 0.001), lower estimated glomerular filtration rate (66.4 vs 74.0 ml/min/1.73 m2p < 0.001), lower LDL-cholesterol (87.1 vs 105.8 mg/dl), and higher rates of atherosclerotic cardiovascular disease (32.7 vs 16.7% p < 0.001). CONCLUSION: Insulin therapy is underprescribed in T2D, with over 1-in-4 people living with T2D not being prescribed insulin despite deficient glycemic control. These findings highlight the need for insulin therapy when glycemic control is inadequate under other interventions.

Underprescription of SGLT2i and GLP-1 RA: CAREPRO-T2D (Cardiorenal Protection in Type 2 Diabetes) Cross-Sectional Study.

BACKGROUND: New glucose-lowering drugs have shown benefits regarding cardiovascular events, heart failure, and kidney-related outcomes in type 2 diabetes (T2D). This study aimed to estimate the adequacy of SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) prescription to people living with T2D with established atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF). MATERIAL AND METHODS: This was a cross-sectional study based on adults with T2D in a Portuguese local health unit between January 2019 and January 2020. Subjects with ASCVD were compared with subjects without ASCVD, and subjects with HF were compared with subjects without HF regarding clinical and demographic characteristics. RESULTS: Our study included 13,869 adults with T2D, among whom 5.9% were coded for HF and 20.4% were defined as having ASCVD. SGLT2i were prescribed to 36.0% of subjects with HF. SGLT2i and/or GLP-1 RA were prescribed to 36.1% of patients with ASCVD. When comparing with subjects without ASCVD, subjects with ASCVD were significantly older (70.8 vs. 66.5 years, p<0.001), had lower estimated glomerular filtration rate (68.2 vs. 74.6 mL/min/1.73 m2, p<0.001), and higher rates of prescription of SGLT2i and/or GLP-1 RA (36.1 vs. 31.4%, p<0.001). When comparing with subjects without HF, subjects with HF were significantly older (74.6 vs. 66.9 years, p<0.001), had lower estimated glomerular filtration rate (59.6 vs. 74.1, mL/min/1.73 m2, p<0.001), and higher rates of prescription of SGLT2i (36.0 vs. 30.3%, p<0.001). CONCLUSION: SGLT2i and GLP-1 RA are underprescribed in T2D, with almost two-thirds of patients not being prescribed these agents despite being strongly advised by current guidelines. These findings highlight the need for specific actions to improve T2D management at primary care level.

Hypoparathyroidism as the single major component for decades of autoimmune polyglandular syndrome type 1.

SUMMARY: Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison's disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison's disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison's disease in combination, the management of APS-1 can be complex. LEARNING POINTS: Autoimmune polyglandular syndrome type 1 (APS-1) is a deeply heterogeneous genetic entity with a broad spectrum of clinical manifestations and a significant intra-family phenotypic variability. Early diagnosis of APS-1 is challenging but clinically relevant, as endocrine and non-endocrine manifestations may occur during its natural history. APS-1 should be considered in cases of acquired hypoparathyroidism, and even more so with manifestations with early onset, family history and consanguinity. APS-1 diagnosis needs a high index of suspicion. Key information such as all the comorbidities and family aspects would never be valued in the absence of a complete clinical history taking. Especially in hypoparathyroidism and Addison's disease in combination, the management of APS-1 can be complex and is not a matter of simply approaching individually each condition. Regular long-term monitoring of APS-1 is essential. Intercalary contact by phone calls benefits the control of the disease and the management of complications.