T he westernised world is in the midst of an epidemic of type 2 diabetes and associated cardiovascular disease. These closely interlinked conditions have a common pathophysiological basis underpinned by insulin resistance and the metabolic syndrome. Contemporary changes in environmental factors on a background of genetic susceptibility are thought to account for the increases seen. Life on earth is governed by the 24-hour environment of light and darkness cycling with the rotation of the earth. Numerous metabolic and physiological pathways are coordinated to this 24-hour cycle by an endogenous clock. Recent epidemiological evidence and animal data suggest that disturbance of circadian rhythms through genetic and environmental influences on the molecular clock is pivotal in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. This review describes current knowledge on the topic.

Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance.

Background: In the light of the increasing burden of non-communicable diseases (NCDs) on health systems in low-and middle-income countries, particularly in Sub-Saharan Africa, context-adapted, cost-effective service delivery models are now required as a matter of urgency. We describe the experience of setting up and organising a nurseled Diabetes Mellitus (DM) and Hypertension (HTN) model of care in rural Zimbabwe, a low-income country with unique socioeconomic challenges and a dual disease burden of HIV and NCDs. Methods: Mirroring the HIV experience, we designed a conceptual framework with 9 key enablers: decentralization of services, integration of care, simplification of management guidelines, mentoring and task-sharing, provision of affordable medicines, quality assured laboratory support, patient empowerment, a dedicated monitoring and evaluation system, and a robust referral system. We selected 9 primary health care clinics (PHC) and two hospitals in Chipinge district and integrated DM and HTN either into the general outpatient department, pre-existing HIV clinics, or an integrated chronic care clinic (ICCC). We provided structured intensive mentoring for staff, using simplified protocols, and disease-specific education for patients. Free medication with differentiated periodic refills and regular monitoring with point of care (POC) glycosylated haemoglobin (HbA1c) were provided. Results: Nurses in 7 PHC facilities and one hospital developed sufficient knowledge and skills to diagnose, initiate treatment and monitor DM and HTN patients, and 3094 patients were registered in the programme (188 with DM only, 2473 with HTN only, 433 with both DM and HTN). Major lessons learned from our experience include: the value of POC devices in the management of diabetes; the pressure on services of the added caseload, exacerbated by the availability of free medications in supported health facilities; and the importance of leadership in the successful implementation of care in health facilities. Conclusion: Our experience demonstrates a model for nurse-led decentralized integrated DM and HTN care in a high HIV prevalence rural, low-income context. Developing a context-adapted efficient model of care is a dynamic process. We present our lessons learned with the intention of sharing experience which may be of value to other public health programme managers.

Research into the molecular clock provides a novel window onto endocrine and metabolic disease. These advances present new avenues for diagnostic and therapeutic strategies.

Background In light of the increasing burden of non-communicable diseases on health systems in low- and middle-income countries, particularly in Sub-Saharan Africa, context adapted cost effective service delivery models are now required as a matter of urgency. Multiple models have thus been trialled across Africa with varying degrees of success. Zimbabwe is a low-income country with unique socio-economic challenges but similar dual disease burden of infectious chronic diseases such as HIV and non-communicable diseases. We aim to describe the experience of setting up and organising a nurse-led Diabetes Mellitus (DM) and Hypertension (HTN) model of care in a rural context of a low-income country from July 2016 to June 2019.Methods A descriptive study based on a conceptual framework successfully applied in the roll-out of antiretroviral therapy in Manicaland Province, Zimbabwe. Attempting to mirror the HIV experience, we describe the key enablers in the design and implementation of the model: decentralization of services, integration of care, simplification of management guidelines, mentoring and task-sharing, provision of affordable medicines, quality assured laboratory support, patient empowerment, a dedicated monitoring and evaluation system, and a robust referral system.Results 11 out of 51 health facilities were selected in Chipinge district, of which nine were primary health care (PHC) clinics and two were hospitals. DM/HTN services were set up and integrated into the general out-patient department or pre-existing HIV clinics. In one hospital, an integrated chronic care clinic was established. Through structured intensive mentoring, including simplified protocols, nurses in seven PHC facilities and one hospital developed sufficient knowledge and skills to diagnose, initiate treatment and monitor DM/HTN patients. Overall, more than 3000 patients were registered in a dedicated recording system and offered education. Free medication with differentiated periodic refills and regular monitoring of blood pressure and/or blood glucose with the use of glycosylated haemoglobin were provided.Conclusion Our experience shows that it is feasible to implement nurse-led decentralized integrated DM/HTN care in a high HIV prevalence rural, low-income context. Developing a context-adapted efficient model of care is a dynamic process.