Pubertal lipid levels are significantly lower in youth with type 1 diabetes who experienced partial clinical remission

Importance: The physiologic changes in lipids during puberty in type 1 diabetes (T1D) is unclear as subjects in previous studies were not stratified by partial clinical remission (PCR) status. Aim: To determine the effect of PCR on lipid changes during puberty in youth with T1D. Subjects and Methods: A retrospective cross-sectional study of 194 subjects consisting of 71 controls of age 12.9±1.3y and 123 subjects with T1D stratified into remitters (n=44, age 13.0±0.8y) and non-remitters (n=79, age 11.2±0.6y). PCR was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. Results: Among the pubertal cohort, low-density lipoprotein cholesterol concentration was significantly higher in the non-remitters compared to the remitters, 91.1±25.6mg/dL vs 77.2±25.8mg/dL, p=0.018; and the normal-weight controls, 91.1±25.6mg/dL vs 70.4±22.9 mg/dL, p=0.009; but was similar between the overweight/obese controls and non-remitters, 89.7±28.9mg/dL vs 91.1± 25.6mg/dL, p=0.81, and similarly between the normal-weight controls and remitters, 70.4±22.9mg/dL vs 77.2±25.8mg/dL, p=0.39. Total cholesterol was also significantly higher in the non-remitters compared to the remitters, 167.8±30.5 mg/dL vs 149.8±32.1mg/dL, p=0.012; and normal-weight controls, 167.8±30.5mg/dL vs 143.2±30.1mg/dL, p=0.011; but similar between the non-remitters and overweight/obese controls, p=0.098; and remitters and normal-weight controls, p=0.51. Non-HDL cholesterol was equally significantly higher in non-remitters compared to remitters, 111.3±30.1mg/dL vs 95.9±29.1mg/dL, p=0.028; and normal-weight controls, 111.3±30.1mg/dL vs 86.2± 32.2mg/dL, p=0.028; but similar between non-remitters and overweight/obese controls, p=0.48; and remitters versus normal-weight controls, p=0.39. Conclusions: Puberty-related reductions in LDL, TC, and non-HDL occur in remitters and normal-weight controls, but not in non-remitters and overweight/obese controls

Data from: Children with type 1 diabetes who experienced a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis

Manuscript abstract: Importance: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized. Aim: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status. Subjects and Methods: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 ± 2.9 years, [male 11.7 ± 2.9 years, (n=55); female 12.0 ± 2.9 years, (n=68), p=0.60] with type 1 diabetes of 4-5 years duration. Anthropometric and biochemical data were collected at the 4th or 5th year after diagnosis in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4-5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin-dose adjusted hemoglobin A1c (IDAA1c) of ≤9. Results: There were 44 (35.8%) remitters (age 13.0 ± 2.5y; male 52.3%). Both the total cholesterol and LDL-cholesterol were significantly lower in remitters compared to non-remitters: LDL-C: 78.8 ± 28.7 mg/dL vs. 91.6 ± 26.5 mg/dL, p=0.023; and total cholesterol: 151.5 ± 32.6 mg/dL vs. 167.0 ± 29.6 mg/dL, p=0.015. Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, body mass index z score, thyroid function, celiac disease occurrence, or vitamin D status. Though a greater number of remitters were in puberty compared to non-remitters (86.4% vs. 60.8%, p=0.006), LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p=0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p=0.018) after adjusting for age and duration of diabetes. Conclusions: Children with type 1 diabetes who underwent a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis regardless of their age, glycemic control, adiposity, or pubertal status. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complication in type 1 diabetes between remitters and non-remitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing non-remission as a non-modifiable risk factor for vascular complication in type 1 diabetes

Children with type 1 diabetes who experienced a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis

IMPORTANCE: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized. AIM: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status. SUBJECTS AND METHODS: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 +/- 2.9 years, [male 11.7 +/- 2.9 years, (n = 55); female 12.0 +/- 2.9 years, (n = 68), p = 0.60] with type 1 diabetes of 4-5 years duration. Anthropometric and biochemical data were collected at the 4th or 5th year after diagnosis in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4-5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin-dose adjusted hemoglobin A1c (IDAA1c) of \u3c /=9. RESULTS: There were 44 (35.8%) remitters (age 13.0 +/- 2.5y; male 52.3%). Both the total cholesterol and LDL-cholesterol were significantly lower in remitters compared to non-remitters: LDL-C: 78.8 +/- 28.7 mg/dL vs. 91.6 +/- 26.5 mg/dL, p = 0.023; and total cholesterol: 151.5 +/- 32.6 mg/dL vs. 167.0 +/- 29.6 mg/dL, p = 0.015. Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, body mass index z score, thyroid function, celiac disease occurrence, or vitamin D status. A greater number of remitters were in puberty compared to non-remitters (86.4% vs. 60.8%, p = 0.006). LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p = 0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p = 0.018) after adjusting for age and duration of diabetes. CONCLUSIONS: Children with type 1 diabetes who underwent a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complication in type 1 diabetes between remitters and non-remitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing non-remission as a non-modifiable risk factor for vascular complication in type 1 diabetes

Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes

Background: Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study\u27s aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 +/- 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 +/- 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 +/- 1.1% vs 8.3 +/- 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 +/- 1.1% vs. 8.7 +/- 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 +/- 0.98% vs. 0.38 +/- 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 +/- 1.4 vs -0.22 +/- 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users

Mechanisms and early patterns of dyslipidemia in pediatric type 1 and type 2 diabetes

Objectives: The is no consensus on the early patterns of lipid-based cardiovascular disease (CVD) risk in youth with either type 1 diabetes (T1D) or type 2 diabetes (T2D). The aim was to determine the differences in CVD risk, using lipid profiles, in children and adolescents with either T1D or T2D at the time of their first lipid assessment, after stratifying the T1D cohort into remitters and non-remitters based on their honeymoon history. Methods: A cross-sectional study of 249 subjects consisting of 73 controls, 53 T2D subjects, and 123 T1D subjects stratified into remitters (n=44), and non-remitters (n=79). Partial clinical remission (PCR) was defined as insulin-dose adjusted HbA1c of \u3c /=9. Pubertal status was determined by Tanner staging. Results: After adjusting for age, sex, BMI, race, and pubertal status, T2D patients had significantly higher LDL-C compared to the controls (p=0.022), the remitters (p=0.029), but not the non-remitters (103.1 +/- 5.9 mg/dL vs. 91.4 +/- 4.2 mg/dL, p=0.49). Similarly, T2D patients had significantly higher non-HDL-C compared to the controls (p=0.006), the remitters (p=0.0002), but not the non-remitters (137.6 +/- 7.1 mg/dL vs. 111.71 +/- 5.0 mg/dL, p=0.053). Total cholesterol was also significantly higher in T2D patients compared to the controls (p=0.0005), the remitters (p=0.006) but not the non-remitters (183.5 +/- 6.6 mg/dL vs. 166.2 +/- 4.8 mg/dL, p=0.27). Conclusions: Lack of the honeymoon phase in children and adolescents with T1D confers early and significantly increased lipid-based cardiovascular risk to these patients that is similar to the elevated cardiovascular risk seen in T2D

Analysis of the changes in serum LDL-cholesterol concentration in the first 4–5 years of type 1 diabetes stratified by both pubertal status and remission status.

<p>LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p = 0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p = 0.018) after adjusting for age and duration of diabetes.</p

Longitudinal assessment of glycemic control in remitters and non-remitters based on the comparison of changes in (a) hemoglobin A1c and (b) total daily dose of insulin at 6 months and at 4–5 years following the diagnosis of type 1 diabetes.

<p>Both the HbA1c and Total daily dose (TDD) of insulin were significantly lower in the remitters at the peak of partial clinical remission (PCR) at 6 months compared to the subsequent values at 4–5 years: TDD, 0.22 ± 0.2 units/kg/day vs. 0.64 ± 0.6 units/kg/day, p<0.001; HbA1c 7.35 ± 1.3% vs. 8.6 ± 1.5%, p = 0.0001 (56.8 ± 14.6 mmol/mol vs. 70.4 ± 16.9 mmol/mol, p = 0.0001). In contrast, there was no difference in HbA1c between 6 months and 4–5 years among the non-remitters; 8.74 ± 1.0% vs. 8.77 ± 1.2, p = 0.57, (72.0 ± 11.1 mmol/mol vs. 72.3 ± 13.5 mmol/mol, p = 0.57).</p

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially