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Type 1 diabetes onset at young age is associated with compromised bone quality.

ABSTRACT: Women with type 1 diabetes (T1D) are at increased risk for fracture. We studied the association of T1D and young age at T1D onset (T1D onset before 20 years) on bone structural quality. 24 postmenopausal women with T1D (mean age 60.9 years, mean T1D duration 41.7 years) and 22 age, sex- and body mass index (BMI)-matched controls underwent dual X-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the lumbar spine, hip and distal radius. Bone mass, geometry and estimated bone strength were assessed at distal and shaft of non-dominant radius and tibia using peripheral quantitative computed tomography (pQCT). Postmenopausal women with T1D had lower trabecular volumetric bone mineral density (vBMD) (LSM ± SEM; 166.1 ± 8.2 vs 195.9 ± 8.3 mg/cm³, p = 0.02) and compressive bone strength (24.6 ± 1.8 vs 30.1 ± 1.9 mg^2/mm⁴, p = 0.04) at the distal radius compared to controls adjusting for age, BMI and radius length. At the distal radius, patients with young onset T1D had lower total vBMD (258.7 ± 19.7 vs 350.8 ± 26.1 mg/cm³, p = 0.02) and trabecular vBMD (141.4 ± 11.6 vs 213.6 ± 15.4 mg/cm³, p = 0.003) compared to adult onset T1D patients adjusting for age, BMI and the radius length. At the tibial shaft, young onset T1D patients had larger endosteal circumference (39.1 ± 1.2 vs 32.1 ± 1.6 mm, p = 0.005) with similar periosteal circumference (67.1 ± 0.9 vs 65.1 ± 1.2 mm, p = 0.2) resulting in reduced cortical thickness (4.4 ± 0.1 vs 5.2 ± 0.1 mm, p = 0.004) compared to adult onset T1D patients adjusting for age, BMI and the tibia length. There was no difference in the lumbar spine, femoral neck, total hip and distal radius DXA-measured aBMD between subjects with T1D and controls. T1D is associated with lower trabecular vBMD at the distal radius. T1D onset before age 20 is associated with cortical bone size deficits at the tibial shaft.

SUBMITTER: Shah VN

PROVIDER: S-EPMC8143874 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.

Project description:BackgroundType 2 diabetes diagnosed during youth and early adulthood is aggressive and associated with a high burden of vascular complications. The increase in complications is often attributed to long disease duration and poor metabolic control. Whether people with young-onset type 2 diabetes are inherently more susceptible to long-term complications than those diagnosed in later adulthood is unclear.MethodsProspective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10-25 years after diabetes diagnosis, were analysed. The cross-sectional associations between age at diagnosis and microvascular and macrovascular complications were analysed using logistic regression models, adjusted for duration of diabetes exposure and metabolic risk factors including blood pressure, cholesterol and updated mean HbA1c .ResultsThe prevalence of retinopathy was highest in those with young-onset type 2 diabetes (diagnosed at age 15 to <40 years). After 10-15 years' diabetes duration, the adjusted odds ratio for retinopathy in this population was 2.8 (95% CI 1.9-4.1; reference group those diagnosed at 60 to <70 years of age). The odds of retinopathy remained higher in people with young-onset type 2 diabetes after longer durations of diabetes exposure; the odds decreased with increasing age at diagnosis. This pattern was not observed in models of other complications: after 10-15 years' diabetes exposure, the adjusted odds ratios for albuminuria, peripheral neuropathy and macrovascular disease in people with young-onset type 2 diabetes were 0.5 (95% CI 0.4-0.8), 0.7 (95% CI 0.5-1.1) and 0.2 (95% CI 0.1-0.3), respectively.ConclusionAfter accounting for disease duration and other important confounders, people with type 2 diabetes diagnosed in youth and early adulthood (or with a younger current age) appeared to be inherently more susceptible to retinopathy. For other complications, adjusted risk appears highest in the oldest age of diagnosis group. These data have screening and treatment target implications.

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Type 1 diabetes onset at young age is associated with compromised bone quality.

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