Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes: Table 1

Cardiovascular risk is increased in adults with type 1 diabetes (T1D), although the mechanism is poorly understood. Endothelial dysfunction may contribute to increased coronary artery calcium (CAC) in T1D, and CAC severity may be associated with reduced nitric oxide (NO) synthesis and/or increased inflammation. We tested the hypotheses that high CAC and T1D are associated with expression of endothelial NO synthase (eNOS, enzyme that produces NO), phosphorylated eNOS (p-eNOS), and NFκB (pro-inflammatory transcription factor). Participants were categorized as having high (>80 Agatston units [AU]) or low CAC (<15 AU), measured by CT scan. Protein expression was measured using quantitative immunofluorescence in endothelial cells harvested from 14 women with T1D (mean age 52±8 years; 7 high CAC); 13 men with T1D (mean age 58±7 years; 5 high CAC); 10 women without diabetes (mean age 61±4 years; 3 high CAC); and 10 men without diabetes (mean age 59±6 years; 4 high CAC). All analyses used ratios of endothelial cell protein expression to control human umbilical vein endothelial cell protein expression. Independent t-tests compared protein expression by sex and T1D. Linear regression tested the associations of high vs. low CAC and T1D with the 3 proteins of interest after adjustment for age and sex. In men, eNOS expression differed by T1D: men with T1D had reduced cytoplasmic (0.34 vs.0.52, p=0.03) and nuclear (0.44 vs. 0.60, p=0.02) eNOS expression compared with men without T1D, suggesting reduced NO synthesis. There were no differences in p-eNOS expression, indicating that eNOS levels were likely not due to differential activation. In women, NFκB expression similarly differed by T1D: women with T1D had higher cytoplasmic (0.81 vs. 0.63, p=0.01) and nuclear (0.99 vs. 0.75, p=0.01) NFκB expression compared with women without T1D, suggesting greater inflammation. After adjustment for age and sex, there was no significant association between high vs. low CAC in endothelial expression of any proteins. The data trend suggested that high vs. low CAC is associated with reduced cytoplasmic (0.36 vs. 0.47, p=0.06) and nuclear (0.48 vs. 0.55, p=0.12) eNOS expression. T1D trended in the same direction for both cytoplasmic (0.36 vs. 0.47, p=0.06) and nuclear (0.47 vs. 0.55, p=0.13) eNOS expression. High vs. low CAC also trended towards an association with greater cytoplasmic (0.72 vs. 0.66, p=0.21) and nuclear (0.85 vs. 0.80, p=0.40) NFκB expression, while T1D was significantly associated with greater cytoplasmic (0.76 vs. 0.63, p=0.006) and nuclear (0.92 vs. 0.73, p=0.003) NFκB expression. Neither CAC nor T1D was associated with p-eNOS expression in linear regression. In conclusion, eNOS and NFκB expression are potential mechanisms for increased CAC given their roles in reduced NO synthesis and increased inflammation, and may differ by sex in people with T1D. Regardless of high CAC, inflammation in T1D is increased.

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Bone Mineral Density across the Lifespan in Patients with Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz153 ◽

2019 ◽

Vol 105 (3) ◽

pp. 746-753 ◽

Cited By ~ 4

Author(s):

Eitan Halper-Stromberg ◽

Tyler Gallo ◽

Anagha Champakanath ◽

Iman Taki ◽

Marian Rewers ◽

...

Keyword(s):

Bone Mineral Density ◽

Body Mass Index ◽

Type 1 Diabetes ◽

Lumbar Spine ◽

Femoral Neck ◽

Postmenopausal Women ◽

Age Groups ◽

Mineral Density ◽

Age And Sex

Abstract Context Fracture risk in people with type 1 diabetes (T1D) is higher than their peers without diabetes. Objective To compare bone mineral density (BMD) across the lifespan in individuals with T1D and age- and sex-matched healthy controls. Design Cross-sectional. Setting Subjects (5–71 years) with T1D and matched controls from ongoing research studies at Barbara Davis Center for Diabetes. Patients or other participants Participants with lumbar spine BMD by dual X-ray absorptiometry (DXA) were divided into 2 groups: children ≤20 years and adults >20 years. Intervention None. Main outcome measures Comparison of BMD by diabetes status across age groups and sex using a linear least squares model adjusted for age and body mass index (body mass index (BMI) for adults; and BMI z-score in children). Results Lumbar spine BMD from 194 patients with T1D and 156 controls were analyzed. There was no difference in age- and BMI-adjusted lumbar spine BMD between patients with T1D and controls: among male children (least squares mean ± standard error of the mean [LSM ± SEM]; 0.80 ± 0.01 vs 0.80 ± 0.02 g/cm2, P = .98) or adults (1.01 ± 0.03 vs 1.01 ± 0.03 g/cm2, P = .95), and female children (0.78 ± 0.02 vs 0.81 ± 0.02 g/cm2, P = .23) or adults (0.98 ± 0.02 vs 1.01 ± 0.02 g/cm2, P = .19). Lumbar spine (0.98 ± 0.02 vs 1.04 ± 0.02 g/cm2, P = .05), femoral neck (0.71 ± 0.02 vs 0.79 ± 0.02 g/cm2, P = .003), and total hip (0.84 ± 0.02 vs 0.91 ± 0.02, P = .005) BMD was lower among postmenopausal women with T1D than postmenopausal women without diabetes. Conclusion Across age groups, lumbar spine BMD was similar in patients with T1D compared with age- and sex-matched participants without diabetes, except postmenopausal females with T1D had lower lumbar spine, femoral neck, and total hip BMD.

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Serum Cystatin C and the Incidence of Hypertension in Type 1 Diabetes Mellitus

American Journal of Hypertension ◽

10.1038/ajh.2010.215 ◽

2011 ◽

Vol 24 (1) ◽

pp. 59-63 ◽

Cited By ~ 3

Author(s):

K. Sahakyan ◽

B. E. K. Klein ◽

K. E. Lee ◽

M. Y. Tsai ◽

R. Klein

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Cystatin C ◽

Serum Cystatin C ◽

Serum Cystatin

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Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes

Diabetic Medicine ◽

10.1111/j.1464-5491.2010.03121.x ◽

2010 ◽

Vol 27 (12) ◽

pp. 1358-1365 ◽

Cited By ~ 34

Author(s):

D. Z. I. Cherney ◽

E. B. Sochett ◽

M. G. Dekker ◽

B. A. Perkins

Keyword(s):

Type 1 Diabetes ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Cystatin C ◽

Filtration Rate ◽

Acute Changes

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Differences in long-term metabolic control and BMI in children with type 1 diabetes on insulin pumps stratified by age and sex

Canadian Journal of Diabetes ◽

10.1016/s1499-2671(09)33196-2 ◽

2009 ◽

Vol 33 (3) ◽

pp. 261

Author(s):

E. Pytka ◽

R. Barnes ◽

A. Bossy ◽

N. Dumouchel

Keyword(s):

Type 1 Diabetes ◽

Metabolic Control ◽

Insulin Pumps ◽

Age And Sex

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Diagnostic value of cystatin c urine level as an early marker of diabetic nephropathy in children with type 1 diabetes mellitus

Kazan medical journal ◽

10.17816/kmj1585 ◽

2013 ◽

Vol 94 (2) ◽

pp. 186-189

Author(s):

A S Senatorova ◽

E G Muratova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Type 1 Diabetes Mellitus ◽

Cystatin C ◽

Urine Excretion ◽

Group 3 ◽

Group 2 ◽

Excretion Level

Aim. To improve the diagnosis of early stages of diabetic nephropathy by examining cystatin C urine excretion in children with type 1 diabetes mellitus. Methods. 83 children aged 11 to 18 years with type 1 diabetes mellitus were included in the study. Children were divided into 3 groups according to the duration of diabetes mellitus: group 1 - 1 to 2 years (n=18), group 2 - 2 to 5 years (n=24), group 3 - over 5 years (n=41). Results. The average values of glycated hemoglobin did not differ significantly between the groups and were assessed as following: group 1 - 8.61±2.1%, group 2 - 8.91±1.5%, group 3 - 8.84±2.5% (p 0,05). Development of «symptomatic» diabetic nephropathy occurred in 10% of children with type 1 diabetes with disease duration over 5 years. Cystatin C urine excretion was the highest in children with long clinical course of type 1 diabetes mellitus (p 0.01). Significant variability of cystatin C urine excretion was observed even in children with diabetes duration of 1 to 2 years. Pairwise comparison of cystatin C urine excretion levels and glycated hemoglobin values of children with type 1 diabetes did not show any statistically significant difference. Conclusion. Cystatin C urine excretion level can be an early marker of kidney damage and depict the state of tubular renal function in children with type 1 diabetes mellitus. Tubular dysfunction in children with type 1 diabetes mellitus might be diagnosed when observed cystatin C urine excretion level is over 21.9±1.4 ng/ml (sensitivity 70%, specificity 60%).

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Risk factors and incidence over time for lower extremity amputations in people with type 1 diabetes: an observational cohort study of 46,088 patients from the Swedish National Diabetes Registry

Diabetologia ◽

10.1007/s00125-021-05550-z ◽

2021 ◽

Author(s):

Sara Hallström ◽

Ann-Marie Svensson ◽

Aldina Pivodic ◽

Arndís F. Ólafsdóttir ◽

Magnus Löndahl ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Lower Extremity ◽

Renal Dysfunction ◽

Diabetes Registry ◽

Male Sex ◽

The Impact ◽

Over Time ◽

Age And Sex

Abstract Aims/hypothesis The aim of this work was to study the incidence over time of lower extremity amputations and determine variables associated with increased risk of amputations in people with type 1 diabetes. Methods Individuals with type 1 diabetes registered in the Swedish National Diabetes Registry with no previous amputation from 1 January 1998 and followed to 2 October 2019 were included. Time-updated Cox regression and gradient of risk per SD were used to evaluate the impact of risk factors on the incidence of amputation. Age- and sex-adjusted incidences were estimated over time. Results Of 46,088 people with type 1 diabetes with no previous amputation (mean age 32.5 years [SD 14.5], 25,354 [55%] male sex), 1519 (3.3%) underwent amputation. Median follow-up was 12.4 years. The standardised incidence for any amputation in 1998–2001 was 2.84 (95% CI 2.32, 3.36) per 1000 person-years and decreased to 1.64 (95% CI 1.38, 1.90) per 1000 person-years in 2017–2019. The incidence for minor and major amputations showed a similar pattern. Hyperglycaemia and renal dysfunction were the strongest risk factors for amputation, followed by older age, male sex, cardiovascular comorbidities, smoking and hypertension. Glycaemic control and age- and sex-adjusted renal function improved during the corresponding time period as amputations decreased. Conclusions/interpretation The incidence of amputation and of the most prominent risk factors for amputation, including renal dysfunction and hyperglycaemia, has improved considerably during recent years for people with type 1 diabetes. This finding has important implications for quality of life, health economics and prognosis regarding CVD, indicating a trend shift in the treatment of type 1 diabetes. Graphical abstract

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Relationship between biochemical parameters and glomerular filtration rate by Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2021-25(2)-13 ◽

2021 ◽

Vol 25 (2) ◽

pp. 261-265

Author(s):

Yu. O. Kryvoviaz

Keyword(s):

Type 1 Diabetes ◽

Glomerular Filtration Rate ◽

Blood Glucose ◽

Correlation Analysis ◽

Cystatin C ◽

Biochemical Parameters ◽

Filtration Rate ◽

Urinary Albumin ◽

General Group

Annotation. The aim of research is to study correlations of biochemical parameters with glomerular filtration rate according to Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes (T1D). 78 men and 62 women aged 22-26 years with T1D were examined. The control group consisted of 8 almost healthy men and 13 almost healthy women of the same age. The level of microalbuminuria and cystatin C was determined in all patients by enzyme-linked immunosorbent assay. Biochemical evaluation of fasting blood glucose, glucose 2 h after exercise, mean value of glucose, creatinine, GFR according to Cockcroft-Gault, CKD EPI and GFR according to cystatin C. Correlation analysis between the series of indicators was calculated using Spearman statistics in the license package “Statistica 5.5”. In patients with T1D, there is no significant correlation in normoalbuminuria between urinary albumin levels and GFR by Cockcroft-Gault (in women), CKD EPI and cystatin C (in all study groups). No significant correlations were found between urinary albumin levels and GFR by Cockcroft-Gault, CKD EPI and cystatin C in the proteinuria group. The correlation analysis revealed in the general group and in women with proteinuria an association between the average value of blood glucose and low GFR levels by Cockcroft-Gault, CKD EPI (negative medium strength correlation r = from -0.31 to -0.46) and elevated creatinine (positive strong correlation r=0.62 and r=0.91), indicating an unfavorable role of hyperglycemia in the development of nephropathy in patients with T1D. Higher correlations of cystatin C with GFR by cystatin C (r= -1.0) than by creatinine with GFR by Cockcroft-Gault (r = from - 0.63 to 0.99) and by CKD EPI (r = from -0.73 to -0.99) were demonstrated. The strength of the correlations increases from GFR by Cockcroft-Gault to GFR by cystatin C. Correlations between creatinine and GFR by Cockcroft-Gault and CKD EPI were characterized by sex differences (greater in women) and an increase in their strength synchronously with an increase in urinary microalbumin. At the same time, there is a consistently high identical value (r= -1.0) of correlations of the level of cystatin C with GFR on cystatin C in all comparison groups. Neither the sex factor nor the degree of albuminuria affected the change in their strength. Only men with microalbuminuria had moderate feedback between creatinine and cystatin C (r= -0.46). In all groups of women, in the general group and in men with normoalbuminuria and proteinuria, the correlations are close to zero, which may indicate the absence of a linear relationship between these indicators. When dividing the sample according to the level of cystatin C between the level of creatinine and the level of cystatin C, the following were found: medium feedback (r= -0.37) in the general group with normoalbuminuria and cystatin C>0.9; moderate feedback (r= -0.37) in the general group and in men with proteinuria and cystatin C<0.9 strong feedback (r= -0.90 and r= -0.88). Thus, in the course of correlation analysis it was found: microalbuminuria is not an independent marker of diabetic nephropathy (DN), starting from preclinical and ending with a clinically manifested stage of this complication; for timely and adequate diagnosis of DN it is necessary to measure the level of albumin, creatinine and cystatin C, which are independent markers of renal dysfunction; cystatin C gives a more accurate approximation to the actual values of GFR than creatinine; cystatin C is more sensitive in the early stages, and creatinine is a marker of later stages of DN development; hyperglycemia is the main initiating metabolic factor in the development and progression of DN.

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Serum Cystatin C as a Biomarker for Early Diabetic Nephropathy and Dyslipidemia in Young Type 1 Diabetes Patients

10.21203/rs.3.rs-91508/v1 ◽

2020 ◽

Author(s):

Lina Radzeviciene ◽

Ingrida Stankute ◽

Ausra Monstaviciene ◽

Rimantė Dobrovolskiene ◽

Evalda Danyte ◽

...

Keyword(s):

Type 1 Diabetes ◽

Kidney Function ◽

Cystatin C ◽

Young Patients ◽

Kidney Injury ◽

Albumin Excretion Rate ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Long Term Follow Up

Abstract Background. Early capture of initial stages of complications is the destination of long term follow up of type 1 diabetes (T1D) patients. The aim of this study was to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients.Methods. 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results. Median age of study subjects was 16.2 years (2.1;26.4), diabetes duration – 5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c <7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine – 63 µmol/L (6;126). Median of eGFRcys was lower than eGFRcreat (92 ml/min/1.73m2 vs. 101 ml/min/1.73m2, p<0.001). 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r=-0.088, p<0.05, as well as cystatin C and HDL, r=-0.097, p<0.01.Conclusion. This study showed that cystatin C might be used as an additional biomarker of early kidney injury for young patients with T1D.

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