Hypoglycaemia in older people with diabetes

Abstract

Diabetes prevalence is increasing in our ageing and increasingly obese society. Diabetes is a heterogeneous condition, and challenges remain in all aspects of its management - from diagnosis through to optimising treatment, to managing complications. Increasing age brings altered physiological responses to disease, treatments and complications - and there may be more wide-ranging considerations such as dietary, mobility, dependency or cognition, to name just a few. Hypoglycaemia is one of the most important potential side-effects of insulin-therapy, and elderly adults are at particular risk from its consequences.

Insulin-treated patients may have long-standing Type 1 diabetes, or have Type 2 diabetes which has progressed to requiring insulin treatment, due to progressive beta cell deficiency. Even within this group of patients, there is heterogeneity, and assessment of risks can be challenging.

Endogenous insulin levels can be assessed by measuring C-peptide. Recent advances in this has meant this is much more practical, enabling assessment of endogenous levels in large numbers of patients more feasible, and hence allowing important questions to be addressed. In the context of older patients, particularly interesting questions are whether patients with long-standing Type 2 diabetes can develop severe insulin deficiency, and whether absolute/severe endogenous insulin levels have an impact on treatment or complications of diabetes within insulin-treated cohorts – such as hypoglycaemia. This may thence raise the question of whether C-peptide measurement could potentially be used as an extra clinical tool for risk assessment in a patient population which can be tricky to manage at times.

The aim of this thesis is thus to explore some of the issues around management of diabetes in the elderly: in particular hypoglycaemia, and use of C-peptide to more fully assess patients and consider a possible role for it in routine clinical care of some patients.

Chapter 1 puts the thesis in context, firstly reviewing hypoglycaemia in the elderly in general, and then considering aspects of endogenous insulin levels and C-peptide measurement.

Chapter 2 addresses the problem of recognition of hypoglycaemia in an elderly population, using primary care records and documented symptoms at consultations. Are we missing hypoglycaemia in this population?

Accurate diagnosis of diabetes is crucial for getting people on the right treatment guidelines, and can be challenging. Chapter 3 uses a spot urine measure of C-peptide to test for the first time the accuracy of the UK Practical Classification Guidelines (published by the Royal College of General Practitioners and NHS Diabetes).

Progressive insulin deficiency in Type 2 diabetes is the main reason people with long-standing Type 2 diabetes may eventually require insulin treatment. Chapter 4 uses the spot urine measure of C-peptide as a screening tool to assess if insulin-treated people with a clinical diagnosis of Type 2 diabetes may develop absolute insulin deficiency.

Even more practical than a spot urine test to measure C-peptide, could be a random non-fasting blood measure of C-peptide, which could thus be measured when patients have their routine blood tests done in the community or outpatient appointments. Chapter 5 looks at how such a measure correlates with the gold-standard mixed meal tolerance test C-peptide measure.

Severe insulin deficiency in Type 1 diabetes has been correlated with increased complications including hypoglycaemia, but the impact of endogenous insulin levels has not been assessed greatly in Type 2 diabetes. Chapter 6 reports a study looking into this possible relationship, using hypoglycaemia questionnaire responses from a large number of community-dwelling insulin-treated adults (of both diagnoses), in the context of their clinical diabetes diagnosis and their random non-fasted blood C-peptide levels.

Chapter 7 assesses in more detail the rates of hypoglycaemia in a small group of insulin-treated patients with a clinical diagnosis of Type 2 diabetes, selected on the basis of their endogenous C-peptide levels. As well as subjective assessment of their hypoglycaemia experience using questionnaires, continuous glucose monitoring was used to objectively assess their rates of hypoglycaemia and glucose variability.

Chapter 8 pulls all the above chapters together, summarising them in the context of other research, discussing their limitations and possible areas for future research, and their implications for now for clinical practice.