Appendix of requested variables

Author
Affiliation

Luke W. Johnston

Steno Diabetes Center Aarhus

Published

October 30, 2024

Danmarks Statistik, Forskningsservice
August 22, 2023
Generel Forskningsservice
Projekt nr. 708421

Projekttitel

Interplay between diabetes and intergenerational transmission of health determinants over the life course

Populations afgrænsning(er)

In create the family structure and linkages, we need:

  • All index individuals born or who migrated into Denmark on or after 1970-01-01.
  • Registers and variables:
    • BEF: AEGTE_ID, CIVST, CIV_VFRA, E_FAELLE_ID, FAR_ID, MOR_ID, PNR, FOED_DAG, KOEN, OPR_LAND.
    • CPST: AEGTEFAELLE_ID, CIVST, CIV_DATO, FAR_ID, MOR_ID, PNR.

Combining BEF and CPST has, from our previous experience and projects, resulted in better coverage in creating our study population than one register alone.

List of registers and variables from DST

List of registers and variables from external sources

Labka

For alle individer i databasen ønskes der laboratorie udtræk af følgene NPU/DNK-koder så langt tilbage i tiden som muligt.

List of requested ICD-8 and -10 codes

Da hovedformålet med projektet er at undersøge prævalensen og incidensen af diabetes, relaterede kardiometaboliske sygdomme samt følgesygdomme (komplikationer) i sociale netværk ønsker vi nedenstående ICD10 samt ICD8 koder. Efter koderne har vi kort redegjort for, hvorfor vi ansøger om netop de listede koder.

Justification for requested disease codes

The overall aim of this project is to identify the contributions of family and early life determinants on the development, management and care of diabetes and the diseases that may arise following a diabetes diagnosis, under a life-course framework. The justification for requesting data on multiple disease areas directly follows the primary aim of this project. We investigate this aim focusing on diabetes as the central disease of interest. Diabetes consists of different subtypes (Type 1, Type 2, LADA, MODY, gestational diabetes, secondary diabetes, rare monogenic forms) each with a different set of risk factors, presentation and pathophysiological characteristics. The familial and social effects that are the subject of this project are likely to be different for each of these diabetes subtypes. E.g. for some types of diabetes, caused predominantly by auto-immune mechanisms, familial associations to other auto-immune diseases are more likely than for type 2 diabetes, which is driven to a strong degree by obesity, low physical activity and insulin resistance.

All forms of diabetes have an increased blood glucose level as their central hallmark, and are associated with major and minor complications. The vascular complications are generally subdivided into large-vessel disease (macrovascular): myocardial infarction, stroke, peripheral vascular disease; and small-vessel disease (diabetic retinopathy, neuropathy nephropathy). The occurrence of these complications is not dependent solely on the elevated glucose levels, but also on disturbance of other metabolic risk factors, familial predisposition and pre-existing conditions. Beyond these classical complications, increasingly links between diabetes and other complications are being recognised: depression, cancer, loss of cognitive function, skin conditions.

An important feature of diabetes is that it can be undetected for several years, and that the diabetic complications can sometimes be the first presentation of the disease. In order to study the occurrence of diabetic complications in the context of family we need to assess the complication status for all traditional and novel diabetic complication.

Adequate treatment of diabetes depends on long-term engagement and motivation of the patient for self-management of different aspects of the disease. The capacity to respond adequately to this challenge depends to a large degree on socio-economic status, including the degree of social support in the direct environment surrounding the patient. These effects occur in interaction with other chronic conditions, including mental health conditions.

The justification for the requested list of conditions falls into four categories:

  1. Diagnosis of diabetes itself, in all its forms and subtypes.
  2. Conditions that are an established cause of diabetes, and diseases which have an emerging association with diabetes, which we wish to investigate
  3. Major and minor complications and other consequences / signs of diabetes
  4. Conditions needed to adjust our analyses for the simultaneous occurrence of other chronic health problems (co-morbidity)

Description of disease and its relation to diabetes

  • Cardiovascular disease is the most common cause of death and disability among people with diabetes The cardiovascular diseases that accompany diabetes include angina, myocardial infarction (heart attack), stroke, peripheral artery disease and congestive heart failure. High blood pressure, high cholesterol, high blood glucose and other risk factors contribute to the increased risk of cardiovascular complications.

  • Eye diseases: Diabetic retinopathy and macular edema are the major eye complications of diabetes; but diabetic eye disease also includes cataract and glaucoma. Furthermore, infections of the eyelid and adnexa are also seen.

  • Neurological and neurodegenerative diseases: Diabetic peripheral and autonomic neuropathy are part of the major diabetic microvascular complications. Furthermore, diabetes has long been linked to vascular dementia; probably mediated through chronic ischaemia, endothelial dysfunction and micro-strokes. In the past decade, increasing evidence has emerged for a shared pathophysiological and aetiological connection between diabetes and Parkinson’s disease, Alzheimer’s disease, dementia, loss of cognitive function.

  • Mental health conditions have been linked to diabetes in different ways. The most established link is between depression and diabetes, both as a cause and a consequence, but also an association with schizophrenia has been observed and is receiving increasing attention. Mental health can deteriorate as a consequence of living with diabetes, and poor mental health, including personality and eating disorders can impair a patient’s ability to cope adequately with the demands (changes in lifestyle, self-measurement and management, self-care) posed by the presence of long-standing diabetes. Consequently, patients with co-morbid diabetes and mental health problems tend to have worse control and outcomes for both conditions. Moreover, mental health conditions also affect people’s abilities to build up and maintain social connections, and they may place strain on family relations, potentially altering their influence on health compared to the general population.

  • Orodental health: There is a well-established link between diabetes and orodental health. Diabetes is a risk factor for periodontal diseases such as gingivitis and periodontitis, and the relation is though to be bidirectional, meaning that not only does diabetes increase the occurrence of orodental problems, but also that orodental conditions may affect the metabolic control of diabetes in diabetic patients.

  • Fractures are associated with diabetes both directly and indirectly (as a consequence of loss of eyesight or loss of sensation in the feet due to diabetic retinopathy and neuropathy). Moreover, fractures, especially in the elderly are a strong cause of co-morbidity and can exacerbate other chronic health problems.

  • Gastro-intestinal diseases:

    • Diabetes is ultimately a disease of imbalance in the carbohydrate metabolism, and is closely linked to lipid metabolism. Besides the liver, there is an increasing insight that the gut plays an important regulatory role. Several mechanisms linked to appetite and satiety have been found to be regulated in feed-back loops involving the gut (particularly the duodenum). This is expressed in the marked improvement in metabolic control seen in patients with diabetes who undergo Roux-en-Y gastric bypass operations and the impact on obesity of a Glucagon-like peptide-1 analogues.
    • Another emerging line of research linking the health of the gut to diabetes is the study of the intestinal microbiome. This emerging field is showing increasingly convincing associations between diet, the composition of the bacterial populations in the gut and obesity, CVD and several metabolic diseases including diabetes. It follows that any condition that causes gut inflammation, and malabsorption, such as Irritable Bower Syndrome, Crohn’s disease or gastric and duodenal ulcers, may affect the intestinal microflora, and through that mechanism diabetes risk.
    • Existing diabetes can also cause gut symptoms; patients with severely disregulated diabetes sometimes present with gastroparesis and constipation, which can be seen as a consequence of failed autonomic regulation of gut motility due to diabetic autonomic neuropathy.

  • Liver diseases: Insulin resistance, a central determinant of type 2 diabetes, is principally determined by insulin resistance in the muscles (peripheral) and in the liver (central). Diseases that affect liver function, through inflammation, fat accumulation, fibrosis or a combination of these mechanisms, have an impact of central insulin resistance. This phenomenon is recognised in the strong relationship between Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) with diabetes and the metabolic syndrome. The central role of the liver, and liver conditions, to diabetes, also provides a conceptual link to other metabolic conditions in which the liver plays a central role, such as iron and lipid metabolism.

  • Kidney diseases: Diabetic kidney disease is one of the main microvascular complications of diabetes, progressing from a mild initial presentation (micro-albuminuria) to advanced (macro-albuminuria) and late stages (end-stage renal disease, ultimately with renal failure and the need for dialysis). Loss of renal function itself (both in the presence and absence of diabetes) is recognised as a risk factor for the development of cardiovascular disease. Diabetic kidney disease thus also provides a direct pathophysiological link to the management of hypertension in people with diabetes.

  • Anaemia and Iron metabolism: Iron metabolism has long been implicated as a causal factor in cardiovascular disease aetiology, but there is mounting evidence pointing to a causal link the occurrence of diabetes. Low iron stores and iron deficiency anaemia can have an impact on the ability to use HbA1c as a valid indicator of average glucose levels over a longer period of time. Anaemia is also a strong indicator of general ill health and should be considered when studying diabetes in a context of multi-morbidity.

  • Skin diseases: Several dermatological conditions, including psoriasis, dermatitis and eczema, are seen more frequently in patients with diabetes. Peripheral neuropathy affects the skin’s ability to activate sweat glands, leading to dry and brittle skin and higher occurrence of skin infections, which exacerbate diabetic foot problems.

  • Infertility: Fertility problems are well known for women with diabetes and male infertility is a likely but less studied consequence of diabetes.

List of requested ATC codes