Janaka Karalliedde

Janaka Karalliedde
King's College London | KCL · Cardiovascular Division

MBBS FRCP PhD

About

104
Publications
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Publications

Publications (104)
Article
Full-text available
Type 2 diabetes (T2D) is a progressive disease, with many individuals eventually requiring basal insulin therapy to maintain glycaemic control. However, there exists considerable therapeutic inertia to the prompt initiation and optimal titration of basal insulin therapy due to barriers that include fear of injections, hypoglycaemia, weight gain, an...
Article
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Background: Uncontrolled hyperglycaemia before and during hospitalisation is a risk factor for adverse outcomes in people with diabetes and SARS-CoV-2 infection. Insulin often at high doses is frequently required to manage hyperglycaemia associated with SARS-CoV-2 infection during hospitalisation. However, there is limited information on the clini...
Article
A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which...
Article
A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which...
Article
Background Diabetic Foot Ulcers (DFUs) are a common and feared complication of type 1 and type 2 diabetes. People with DFUs often present a significant clinical complexity due to multimorbidity, frailty, polypharmacy, and disabling conditions. Frailty, defined using the accumulation of health deficits model, has shown to predict worsening health st...
Article
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Diabetic kidney disease accounts for over 40% cases of chronic kidney disease globally. Hypertension is a major risk factor for progression of diabetic kidney disease and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of diabetic kid...
Article
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People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been...
Article
Purpose Diabetic foot ulcers (DFUs) and cardiac autonomic neuropathy (CAN) are severe complications of diabetes mellitus (DM). Both DFU and CAN are associated with increased risk of major cardiovascular events and mortality. Because of the clinical impact of both these conditions, it is important to establish what effect the presence of CAN has on...
Article
Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19...
Article
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Background This study evaluated the cost effectiveness of an intensive lifestyle modification (LSM) intervention delivered by peer educators for the prevention of type 2 diabetes mellitus in a young at-risk population in a low healthcare resource setting.Objective The aim of this study was to evaluate the short-term and long-term cost effectiveness...
Article
Approximately 3.8 million people in the UK have type 2 diabetes mellitus (T2DM) and are, as a consequence, at risk of developing micro- and macrovascular disease. The rapid increase in T2DM prevalence places a considerable burden on secondary healthcare. New classes of glucose-lowering medications (sodium-glucose co-transporter 2 inhibitors and glu...
Article
People with type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular disease (CVD) and kidney disease. This enhanced cardio-renal risk persists despite improvements in care and treatments over the last 20 years. Intensive glucose control alone does not substantially reduce the risk of CVD and end stage kidney disease (ESKD). Ho...
Article
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A 26-year-old Caucasian female with no past medical history or family history of auto-immune disease presented to the emergency department with new onset painless left foot drop. A panel of blood tests revealed blood glucose of 49.9 mmol/L and raised blood ketone levels. The patient was referred to the diabetes team who made a clinical diagnosis of...
Article
To our knowledge, there are no studies examining eGFR trajectories in an ethnically diverse cohort of T2DM patients with established DKD and long follow-up. We conducted a retrospective analysis of medical records of T2DM patients attending a specialist diabetes renal clinic in order to identify risk factors and specific eGFR trajectories associate...
Article
Post‐transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabete...
Article
Background and Aims: Active vitamin D [1,25(OH)2D3] deficiency is a potential modifiable risk factor for cardiovascular (CVD) and renal disease in patients with type 2 diabetes (T2DM) and stage 3/4 chronic kidney disease (CKD). Exact mechanisms are unclear. Arterial stiffness is an independent predictor of CVD. There is limited data on the effect o...
Article
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Background Klotho is a circulating anti-ageing hormone that predicts progression of cardiovascular and renal disease. The role of Klotho in diabetic retinopathy is unknown. Methods We performed a single-centre observational study of 81 people (males 62%) with type 2 diabetes followed for a median of 44 months. Circulating levels of Klotho and othe...
Article
In our study of 187 patients with diabetes hospitalised with COVID-19 we observed a more than 5 fold increased risk of intubation in patients with diabetic retinopathy. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.
Article
Full-text available
The kidney plays a major physiological role in glucose homeostasis but also contributes to the pathophysiology of type 2 diabetes (T2D), mediated by renal sodium glucose cotransporters (SGLTs). This recognition led to development of SGLT2 inhibitors that inhibit proximal renal tubular renal glucose and sodium reabsorption. The glucoretic and natriu...
Article
End stage renal disease (ESRD) is associated with a high mortality rate among patient hospitalised with COVID‐19. To our knowledge, there is limited data on the clinical features, ethnicity, inpatient glycaemic control and outcomes in patients with diabetes related ESRD in the literature. We report the clinical features and outcomes of 39 consecuti...
Article
Aims People with diabetes and peripheral neuropathy (DPN) are at high risk of diabetic foot ulceration (DFU). The prevalence of cardiac autonomic neuropathy (CAN) in people with DFU is unknown and if CAN influences DFU healing is unclear. Methods We investigated, in a prospective observational single-centre cohort study, if CAN predicts DFU healing...
Article
Full-text available
Aims: Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) are affected by renal function in a pre-specified subgroup analysis from the BRIGHT trial....
Article
Full-text available
Background: Diabetes is one of the leading causes of chronic kidney disease (CKD) worldwide. CKD is directly linked to increased morbidity and mortality. The role of vascular changes in diabetes and underlying mechanism of kidney disease is not well understood. Methods: We present a mathematical model of the small arteries in the kidney incorporati...
Article
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Background: We have previously demonstrated in the DIABRISK-SL trial that a trimonthly pragmatic lifestyle modification (P-LSM), as compared to a 12-monthly LSM advice (C-LSM), significantly reduced the primary composite endpoint of predictors of cardio-metabolic disease (new onset type 2 diabetes (T2DM), hypertension, impaired glucose tolerance (...
Article
Background Patients with diabetes and kidney disease are at risk of diabetes-related foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown. Methods We evaluated the incidence of new onset DFU post SPK and KO transplant in 235 patients with diabetic kidney disease and diab...
Article
Diabetic nephropathy is a major underlying cause of morbidity and mortality in both type 1 and type 2 diabetes mellitus. It is strongly associated with cardiovascular disease, particularly heart failure, the incidence of which is about 15-fold greater in patients with diabetic nephropathy. All-cause mortality in patients with diabetic nephropathy i...
Data
Table S1. Comorbidities at baseline (randomized population). Table S2. eGFR by study and in pooled population. Table S3. Concomitant medications at month 6 (pooled randomized population). Table S4. Change in FPG and insulin dose from baseline, by renal function subgroup (pooled mITT population). Table S5. Percentage of participants achieving ta...
Article
Aims To assess the prevalence of risk factors for obstructive sleep apnoea in people with diabetic foot ulcers and to determine whether this risk predicts diabetic foot ulcer healing. Methods We studied 94 consecutive people (69% men) with diabetic foot ulcers (Type 2 diabetes, n=66, Type 1 diabetes, n=28) attending a university hospital foot unit...
Article
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Aims Impaired renal function increases hypoglycemia risk in type 2 diabetes (T2DM). Insulin glargine 300 U/mL (Gla‐300) has previously demonstrated reduced hypoglycemia risk versus insulin glargine 100 U/mL (Gla‐100). Therefore, we investigated the impact of renal function on the safety and efficacy of Gla‐300 and Gla‐100. Materials and Methods A...
Article
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Context and Objective Soluble Klotho (sKlotho) is a circulating hormone with cardiovascular-renal protective effects. Whether sKlotho predicts estimated glomerular filtration rate (eGFR) decline in type 2 diabetes mellitus (T2DM) patients with relatively preserved renal function is unknown. Design, setting, participants and measurements Single-cen...
Article
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Background There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new o...
Article
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Background: People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of infor...
Article
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Background The objective of this study was to evaluate whether aortic pulse wave velocity (Ao‐PWV) predicts estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus. Methods and Results This prospective single‐center cohort study investigated 211 type 2 diabetes mellitus patients with eGFR ≥45 mL/min with a bas...
Article
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Aims/hypothesis: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble K...
Article
We describe a case of a delayed diagnosis of Pendred syndrome. The patient had a history of hearing loss from childhood and presented to the endocrine clinic when aged 32 with an enlarging goitre. The characteristic Mondini deformity was noted on auditory canal MRI scan. Genetic tests confirmed the diagnosis. Pendred syndrome is an autosomal recess...
Article
The objectives of a stage-matched approach to lifestyle change are that individuals progress forward through the stages of change. It also posits that progression through the stages of change is associated with positive changes in lifestyle behaviours. Measuring the relationship between stage of change and food intake is challenging due to the plur...
Article
South Asian populations are predisposed to early onset of the metabolic syndrome. Lifestyle intervention programmes have demonstrated a reduction in the metabolic syndrome and CVD risk; however, the most effective components of the multi-faceted lifestyle interventions are unknown. We studied 2637 Sri Lankan males ( n 1237) and females ( n 1380), w...
Article
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Diabetic renal disease is associated with increased cardiovascular risk and is one of the leading causes of end-stage renal disease worldwide. A combination of hyperglycaemia and hypertension drives the development and progression of diabetic renal disease, with glomerular hyperfiltration being an early manifestation of the disease process. Sodiumg...
Article
Full-text available
Diabetic kidney disease represents a considerable burden; around one-third of patients with type 2 diabetes develop chronic kidney disease. In health, the kidneys play an important role in the regulation of glucose homeostasis via glucose utilization, gluconeogenesis and glucose reabsorption. In patients with diabetes, renal glucose homeostasis is...
Article
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The authors of a new study report that independent of renal disease, any level of glycaemia is associated with increased mortality risk in patients with type 1 diabetes mellitus. However, this view may be overly simplistic - a multifactorial approach is required to reduce excess mortality in this population.
Article
Diabetes mellitus (DM) is increasingly recognized as a heterogeneous condition. The individualization of care and treatment necessitates an understanding of the individual patient's pathophysiology of DM that underpins their DM classification and clinical presentation. Classical type-2 diabetes mellitus is due to a combination of insulin resistance...
Article
Diabetic nephropathy is a major underlying cause of morbidity and mortality in both type 1 and type 2 diabetes mellitus, giving rise principally to cardiovascular disease, in particular heart failure, the incidence of which is about 15-fold greater in patients with diabetic kidney disease. The all-cause mortality in patients with diabetic nephropat...
Article
This work provides a multidimensional method for the simultaneous, direct quantification of intact human insulin and five insulin analogs in human plasma. This investigation solves both the selectivity and sensitivity problems encountered for accurate quantification of insulins in plasma since the former is not possible with conventional assays and...
Article
Full-text available
Background: Soluble Klotho is an anti-ageing phosphaturic protein associated with cardiovascular and renal protection. In-vitro and in-vivo studies have demonstrated that rennin-angiotensin-system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic-kidney-disease (DKD) is unknown. M...
Article
Full-text available
Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown. Plasma-soluble Klotho was...
Article
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Background and objectives: Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC)-mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear. Design, setting, participants, & measurements: In...
Article
Full-text available
South-Asian's are predisposed to early onset type 2 diabetes (T2DM). The prevalence of cardio-metabolic risk-factors in young Sri-Lankans is unknown. To determine by questionnaire and anthropometry the prevalence of first degree family history (FH) of T2DM, physical inactivity, raised waist circumference (WC) and raised body mass index (BMI) in a r...
Data
Full-text available
Screening questionnaire used to determine first degree FH of T2DM, physical activity of the individual participants and to enter height, weight and waist circumference measurements. (PDF)
Data
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Letter of ethical approval for the study. (PDF)
Article
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Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disea...
Data
Screening questionnaire. Screening questionnaire used to determine first degree family history of T2DM and the physical activity of the individual participants.
Article
Full-text available
Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly) l...
Article
Full-text available
Subjects with Polycystic ovarian syndrome (PCOS) are at increased risk of Type 2 diabetes mellitus (T2DM). The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC) are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness pre...