Prevalence and Incidence of Complications of Type One Diabetes in pUne at a Tertiary Care centRE

Type 1 Diabetes Mellitus Clinical Trial

— PICTURE  

Official title:

A Study to Assess Prevalence and Incidence of Long-term Complications of Type 1 Diabetes in a Tertiary Clinic in Pune.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03069196
• Other study ID #: PhD 19
• Status: Active, not recruiting
• Start date: June 10, 2016
• Est. completion date: June 30, 2021

Study information

• Verified date: February 2021
• Source: Kem Hospital, Pune, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Due to early diagnosis (<20yrs of age) of Type 1 Diabetes, patients face longer duration of disease and greater glycemic exposure which makes them more vulnerable towards chronic complications. The aim of this study is to investigate the prevalence and incidence of micro and macro-vascular, pulmonary complications and patterns of growth failure in approximately 500 Type 1 Diabetes patients enrolled at Diabetes Unit, King Edward Memorial Hospital Research Centre. Then follow up of 100 participants who are above 15 years of age at baseline will be done after 2 years to document incidence and progression of complications. This will contribute in assessing the public health burden of complications of Type 1 Diabetes.

Factors associated with prevalence of complications will be investigated. This risk factor analysis could aid in further modifying current prevention and treatment recommendations of these complications. Results of this study could modify current clinical practice.

Description:

BACKGROUND & RATIONALE OF THE STUDY:

Type 1 Diabetes (T1D) is characterized by progressive destruction of insulin secreting pancreatic β-cells. The commonest mechanism involves autoimmunity to components of β-cells. As per International Diabetes Federation report 2013, India houses 67,700 children (<15yrs) with T1D. It also states an approximate figure of 10,900 newly diagnosed T1D children (<15yrs) per year. India accounts for highest number of children with T1D in South East Asian Region. Karnataka Diabetes Registry of T1D patients (1995 to 2008) reported an incidence of 3.8per 100,000 persons in India which is less when compared to Europe and other Western countries. Same study also reported that there is a huge gap between international standard of care and practice in India and that majority of T1D patients don't attain their glycemic targets.

Despite such unfavorable statistics, T1D does not receive adequate attention in terms of clinical and epidemiological research, achieving standards of practice and training of Medical practitioners. Many a times, it is also quoted as "Poor Cousin of Type 2 Diabetes".

A salient feature of T1D is its early onset and diagnosis (<20yrs of age) compared to type 2 diabetes. Consequently patients face longer duration of disease and greater glycemic exposure by the time they reach productive age and suffer chronic complications which are broadly classified into:

1. Microvascular (retinopathy, neuropathy, and nephropathy) and

2. Macrovascular [coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral vascular disease (PVD)] .

These complications contribute to poor quality, substantial morbidity and premature mortality during prime years of life and premature death in T1D patients.

Limited studies are available from India on micro and macro-vascular complication of T1D.

Previous studies have detected that atherosclerotic process is accelerated in T1D population and western studies demonstrated a premature thickening of arterial Intima Media Thickness (IMT) within a short disease duration. Schuyler et al in 1976 for the first time suggested pulmonary complications among T1D. Since then limited attention has been given to lung as a target organ of diabetes even when lungs have a large vascular network. Studies have reported peripheral airway dysfunction and restrictive impairment of lung function even in the absence of smoking, allergies and other causes of airflow destruction among T1D patients. Screening for pulmonary complications among patients with T1D is currently not included in routine clinical settings. Growth parameters like standing height, weight are important indicators of a child's overall health and T1D patients are at an increased risk of developing growth failure. This is due to the role of insulin as a main regulator of Growth Hormone/Insulin Growth Factors (GH/IGF) axis and presence of portal insulin insufficiency among T1D patients. A recent study from Pune reported compromised growth in diabetic children when compared to matched controls. Impaired pre-pubertal and pubertal growth in children and adolescents has been reported in many studies. Factors like gender, age at diagnosis, puberty, metabolic control, insulin regime all affect growth. Bonfig et al 2012 observed a negative association between degree of metabolic control and impaired growth.

Risk factors for complications of T1D have been studied in Western population. Most of them report duration of disease, hyperglycemia, hypertension and dyslipidemia as predictors for micro and macro-vascular complications. But surprisingly "the 50-yr Medalist study" found no association of glycemic control with prevalence of micro-vascular complications.

Research Gap:

The public health burden of T1D is increasing in India and cannot be ignored. Studies assessing long-term complications of T1D from India are limited. They have relatively small sample size, are cross-sectional and retrospective in design. Incidence and progression of these complications has not been reported from India.Prevalence and progression of pulmonary complication among T1D patients has not been studied. Growth data in T1D patients is also limited and will benefit from our study.

Aims and Objectives :

Aim: This thesis will investigate prevalence; incidence and progression of micro-vascular, macro-vascular, pulmonary complications and growth failure among T1D patients in a clinic setting (specialty Diabetes Unit).

1. OBJECTIVE 1 : To determine the prevalence of long-term complications among T1D patients.

2. OBJECTIVE 2 : To determine the impact of factors like age, socio-economic status, body mass index (BMI), body fat (adiposity), duration of disease and glycemic control on the prevalence of complications.

3. OBJECTIVE 3 :To document clinical progression of these complications in duration of 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 323
• Est. completion date: June 30, 2021
• Est. primary completion date: August 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Type 1 Diabetes with a duration of diabetes more than 1 year.

• Willingness to participate in the study and sign the consent form.

• Age : all age groups

• Gender : Both

Exclusion Criteria:

• Other forms of diabetes like Type 2 Diabetes, Gestational Diabetes, Fibro Calculus Pancreatic Disease (FCPD), Mature Onset of Diabetes in Young (MODY) etc.

• People with acute stages of diseases like pneumonia after being treated for the condition.

• Advanced end stage conditions like Cancer etc.

• Pregnant and lactating women

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Locations

Country	Name	City	State
India	Diabetes Unit, Kem Hospital Research Centre	Pune	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Kem Hospital, Pune, India

Country where clinical trial is conducted

India, 

References & Publications (23)

Amutha A, Thai K, Vishwanathan M. Childhood and Adolescent ONset Type 1 Diabetes in India. MGM Journal of Medical Sciences. 2013; 1(1): p. 46-53.

Billow A, Anjana RM, Ngai M, Amutha A, Pradeepa R, Jebarani S, Unnikrishnan R, Michael E, Mohan V. Prevalence and clinical profile of metabolic syndrome among type 1 diabetes mellitus patients in southern India. J Diabetes Complications. 2015 Jul;29(5):659-64. doi: 10.1016/j.jdiacomp.2015.03.014. Epub 2015 Apr 6. — View Citation

Bonfig W, Kapellen T, Dost A, Fritsch M, Rohrer T, Wolf J, Holl RW; Diabetes Patienten Verlaufsdokumentationssystem Initiative of the German Working Group for Pediatric Diabetology and the German Bundesministerium für Bildung und Forschung Competence Net for Diabetes Mellitus. Growth in children and adolescents with type 1 diabetes. J Pediatr. 2012 Jun;160(6):900-3.e2. doi: 10.1016/j.jpeds.2011.12.007. Epub 2012 Jan 11. — View Citation

Dawson SI, Willis J, Florkowski CM, Scott RS. Cause-specific mortality in insulin-treated diabetic patients: a 20-year follow-up. Diabetes Res Clin Pract. 2008 Apr;80(1):16-23. doi: 10.1016/j.diabres.2007.10.034. Epub 2008 Mar 7. — View Citation

Giannini C, Mohn A, Chiarelli F. Growth abnormalities in children with type 1 diabetes, juvenile chronic arthritis, and asthma. Int J Endocrinol. 2014;2014:265954. doi: 10.1155/2014/265954. Epub 2014 Feb 4. Review. — View Citation

Goldman MD. Lung dysfunction in diabetes. Diabetes Care. 2003 Jun;26(6):1915-8. Review. — View Citation

Grauslund J, Jørgensen TM, Nybo M, Green A, Rasmussen LM, Sjølie AK. Risk factors for mortality and ischemic heart disease in patients with long-term type 1 diabetes. J Diabetes Complications. 2010 Jul-Aug;24(4):223-8. doi: 10.1016/j.jdiacomp.2009.05.003. Epub 2009 Jul 3. — View Citation

Keenan HA, Costacou T, Sun JK, Doria A, Cavellerano J, Coney J, Orchard TJ, Aiello LP, King GL. Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year medalist study. Diabetes Care. 2007 Aug;30(8):1995-7. Epub 2007 May 16. — View Citation

Khadilkar VV, Parthasarathy LS, Mallade BB, Khadilkar AV, Chiplonkar SA, Borade AB. Growth status of children and adolescents with type 1 diabetes mellitus. Indian J Endocrinol Metab. 2013 Nov;17(6):1057-60. doi: 10.4103/2230-8210.122623. — View Citation

Kumar KM, Azad K, Zabeen B, Kalra S. Type 1 diabetes in children: Fighting for a place under the sun. Indian J Endocrinol Metab. 2012 Mar;16 Suppl 1:S1-3. doi: 10.4103/2230-8210.94241. — View Citation

Kumar KM. Incidence trends for childhood type 1 diabetes in India. Indian J Endocrinol Metab. 2015 Apr;19(Suppl 1):S34-5. doi: 10.4103/2230-8210.155378. — View Citation

Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003 Jun;46(6):760-5. Epub 2003 May 28. — View Citation

Patterson C, Guariguata L, Dahlquist G, Soltész G, Ogle G, Silink M. Diabetes in the young - a global view and worldwide estimates of numbers of children with type 1 diabetes. Diabetes Res Clin Pract. 2014 Feb;103(2):161-75. doi: 10.1016/j.diabres.2013.11.005. Epub 2013 Dec 1. — View Citation

Pickup, John C and Williams, Gareth, MD Textbook of diabetes (3rd ed). Blackwell Science, Malden, Mass. ; Oxford, U.K, 2003.

Pitocco D, Fuso L, Conte EG, Zaccardi F, Condoluci C, Scavone G, Incalzi RA, Ghirlanda G. The diabetic lung--a new target organ? Rev Diabet Stud. 2012 Spring;9(1):23-35. doi: 10.1900/RDS.2012.9.23. Epub 2012 May 10. Review. — View Citation

Ramachandran A, Snehalatha C, Sasikala R, Satyavani K, Vijay V. Vascular complications in young Asian Indian patients with type 1 diabetes mellitus. Diabetes Res Clin Pract. 2000 Apr;48(1):51-6. — View Citation

Schuyler MR, Niewoehner DE, Inkley SR, Kohn R. Abnormal lung elasticity in juvenile diabetes mellitus. Am Rev Respir Dis. 1976 Jan;113(1):37-41. — View Citation

Singh TP, Groehn H, Kazmers A. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 2003 Feb 19;41(4):661-5. — View Citation

Stakos DA, Schuster DP, Sparks EA, Wooley CF, Osei K, Boudoulas H. Cardiovascular effects of type 1 diabetes mellitus in children. Angiology. 2005 May-Jun;56(3):311-7. — View Citation

Unnikrishnan AG, Bhatia E, Bhatia V, Bhadada SK, Sahay RK, Kannan A, Kumaravel V, Sarma D, Ganapathy B, Thomas N, John M, Jayakumar RV, Kumar H, Nair V, Sanjeevi CB. Type 1 diabetes versus type 2 diabetes with onset in persons younger than 20 years of age. Ann N Y Acad Sci. 2008 Dec;1150:239-44. doi: 10.1196/annals.1447.056. — View Citation

van den Borst B, Gosker HR, Zeegers MP, Schols AM. Pulmonary function in diabetes: a metaanalysis. Chest. 2010 Aug;138(2):393-406. doi: 10.1378/chest.09-2622. Epub 2010 Mar 26. — View Citation

Walsh MG, Zgibor J, Borch-Johnsen K, Orchard TJ; DiaMond Investigators. A multinational comparison of complications assessment in type 1 diabetes: the DiaMond substudy of complications (DiaComp) level 2. Diabetes Care. 2004 Jul;27(7):1610-7. — View Citation

Ziegler AG, Nepom GT. Prediction and pathogenesis in type 1 diabetes. Immunity. 2010 Apr 23;32(4):468-78. doi: 10.1016/j.immuni.2010.03.018. Review. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of Micro-vascular Complications.	Following tests will be performed for micro-vascular complications : RETINOPATHY: Retina scan images; NEPHROPATHY:Urine Albumin : Creatinine ratio), Serum Creatinine, estimated glomerular filtration rate (eGFR); NEUROPATHY : Michigan Neuropathy Screening Instrument (MNSI) and Biothesiometer.; Pulmonary : Spirometry; Prevalence will be reported as percentage i.e. number of cases divided by total number of study participants , multiplied by 100.	Assessed in one day, approximately.
Primary	Prevalence of Macro-vascular Complications.	Following tests will be performed for macro-vascular complications : Cardio-Vascular Disease :Blood pressure, Biochemical tests: Lipid Profile [Triglycerides, Cholesterol (HDL, LDL, total)] and ECG (Electrocardiogram > 15 years of age); Peripheral Vascular Disease : Ankle Brachial Index by Periscope; Prevalence will be reported as percentage i.e. number of cases divided by total number of study participants , multiplied by 100.	Assessed in one day, approximately.
Primary	Prevalence of Growth Complications.	Whole body Anthropometry and Pubertal staging by Tanner's method.	Assessed in one day, approximately.
Primary	Incidence of Micro-vascular, Macro-Vascular and Pulmonary Complications.	Same tools as listed for primary objective 1 will be utilised for measuring incidence of these complications.; - Incidence will be reported as number of new cases per year.	Assessed in one day, approximately.
Primary	Progression of Micro-vascular, Macro-Vascular and Pulmonary Complications.	Same tools as listed for primary objective 1 will be utilised for measuring incidence of these complications.; - Incidence will be reported as number of new cases per year.	Assessed in one day, approximately.
Secondary	Association of Risk factors with prevalence of complications.	Risk factors are : BMI, Body fat, duration of disease, glycemic control (HbA1C), clinical history, family history, socio-economic status, Lifestyle related: Diet, Physical Activity and substance abuse, Body Composition : whole body Anthropometry and Dual Energy X-ray absorptiometry (DXA).; Risk factors will be used for multivariate analysis with the incidence and prevalence rates, also to report relative risks.	All this data will be collected at the time of primary objective 1 i.e. in one day.