Presentation on theme: "Dr Mick Kumwenda MSc FRCP (London) Consultant Nephrologist and Clinical Director (Medicine) Glan Clwyd Hospital Rhyl Denbighshire UK"— Presentation transcript:
Dr Mick Kumwenda MSc FRCP (London) Consultant Nephrologist and Clinical Director (Medicine) Glan Clwyd Hospital Rhyl Denbighshire UK
We are delighted to present you with the highlights this year from yet again a very successful congress attended by 2003 multidisciplinary delegates from around the globe. We wish to thank all those who attended and hope you left the congress full of knowledge that made a difference when you returned back to your home base. We also thank all the speakers that contributed, the quality of all the papers was exceptional and we have selected a few slides with the kind permission of the presenters to summarise key messages from the congress.
The PACD continues to serve the diabetes health care providers in the Middle East as an academic forum for the exchange of knowledge, training and experience. Conference chair : Sherif Hafez Vice chairs: Mohamed Fahmy Abdel-Aziz Megahed Abou El-Magd Assistant Secretary General: Gamela Nasr Hyam Refaat Tantawi
Type 2 diabetes (T2D) is a complex disorder that is affected by multiple genetic and environmental factors. Existing genetic markers explain only a modest (15%) part of the heritability of T2D.
Epigenetics has been defined as heritable changes in gene function that occur without a change in the nucleotide sequence. i e Non -sequence dependent inheritance
It has recently been suggested that glucose availability can affect histone acetylation in an ATP-citrate lyase-dependent manner, further linking energy metabolism to epigenetic regulation
The effectors of innate and adaptive immune cells implicated in maintaining energy balance include: - Macrophages(MQ) - T cells - Neutrophils - Dendritic cells(DCs) - Mast cells (MCs) - Eosinophil's - Natural Killer (NK ) cells - Natural killer T(NKT) cells
(Schwartz, M.W. et al., 2013)
Obesity and life expectancy ● January 2003 Life Table analysis of Framingham Data ● Obese at 40 live 6 to 7 years less than normal ● Overweight at 40 live 3 years less than normal ● Obese smoker live 14 years less than normal
Insulin Resistance Type 2 Diabetes -cell Dysfunction Insulin Resistance Hyperglycaemia Insulin Concentration Insulin Action Euglycaemia -cell Failure Normal IGT ± Obesity Diagnosis of type 2 diabetes Progression of type 2 diabetes DeFronzo et al. Diabetes Care 1992;15:318-68
Guiding principles for nutrition education Patients are responsible Patients are therefore the final decision- makers Knowing what is best for diabetes, is not the same as knowing what is best for that patient These principles have re-defined how we provide education Both structured education and one to one approach benefits patients.
Lifestyle Changes Malmo Study Da Qing Study Finnish Diabetes Prevention Study Diabetes Prevention Program Medications Diabetes Prevention Program : metformin TRIPOD: troglitazone PIPOD: pioglitazone STOP-NIDDM: acarbose NAVIGATOR: nateglinide and valsartan DREAM: rosiglitazone and ramipril XENDOS: orlistat ORIGIN: glargine insulin ACT NOW : pioglitazone TRIPOD=Troglitazone in Prevention of Diabetes Study; PIPOD= Pioglitazone in Prevention of Diabetes Study; STOP-NIDDM=Study to Prevent Non–Insulin-Dependent Diabetes Mellitus; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; DREAM=Diabetes Reduction Approaches with Ramipril and Rosiglitazone; XENDOS=Xenical in the Prevention of Diabetes in Obese Subjects; ORIGIN=Outcomes Reduction with Initial Glargine Introduction.
ADA/EASD position statement 2012 Towards personalized glycaemic targets
ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S27. Figure 2; adapted with permission from Inzucchi SE, et al. Diabetes Care 2012;35:1364–1369
METFORMIN The A1C and ABCDE of glycaemia management in type 2 diabetes: a physician's personalized approach. AGE (years) COMPLICATIONS DURATION>10yrs HbA1c (%) HbA1c≥ 9% HbA1c< 9% Insulin treatment > <6<6.5<7< Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S. The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach. Diabetes Metab Res Rev May;26(4):
Diabetes duration (years) 1.Raskin et al. Diabetes Care 2005;28:260–5 2.Kann et al. Exp Clin Endo Diab 2006; 114:527–32 3.Valensi et al. Int J Clin Pract 2009;63:522–31 4.Oyer et al. Am J Med 2009;122:1043–9 5.Yang et al. Diabetes Care 2008;31:852–6 INITIATEplus Baseline HbA 1c (%) INITIATE 1 EuroMix 2 9.2% IMPROVE TM 3 9.7% 9.2% 9.9% % % 8.6 A1chieve Egypt sub-group
Regime Insulin and SU – 7 studies Insulin and metformin – 4 studies Insulin and TZD – 2 studies Glycated Hb reduction vs insulin alone - 0.4% - 1.3% Yki Jarvinen H Diabetes Care :
< mmol/L (<63-72 mg/dL) Whipple’s triad: ① Symptoms ② Low blood glucose ③ Relief of symptoms when blood glucose raised
197 studies identified Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p<0.001) but no significant reduction in HbA1c (absolute reduction 0.11%, p=0.42). No reported trials included cardiovascular outcomes 12
Prevention of nocturnal hypoglycemia? Reduce postprandial hyperglycemia Raju B, et al. J Clin Endocrinol Metab Jun;91(6): Riccardi G, et al. Diabet Med Mar;16(3):
Potential insulin sparing role in overweight patients with type 1 diabetes. Mixed effects on progression of diabetes reported Strowig SM, Raskin P. Diabetes Care Jul;28(7): Shimada A, et al. Diabetes Metab Res Rev Nov;27(8):951 Yang Z, et al. Diabetes Res Clin Pract Jan;83(1):
Hari Kumar KV, Shaikh A, Prusty P. Diabetes Res Clin Pract May;100(2):e55-8 2
Oral hypoglycemic agents Short acting insulin SUs Take twice daily at suhur and iftar Short acting insulin SUs Take twice daily at suhur and iftar TZDs No treatment adjustment required 2–4 weeks to exert substantial antihyperglycemic effects TZDs No treatment adjustment required 2–4 weeks to exert substantial antihyperglycemic effects DPP4 inhibitors The best tolerated drugs, Consider DPP4i as an alternative to SUs if the risk of hypoglycemia is high DPP4 inhibitors The best tolerated drugs, Consider DPP4i as an alternative to SUs if the risk of hypoglycemia is high SUs Unsuitable for use during fasting because of the inherent risk of Hypoglycemia, use with caution. Consider dose adjustment. SUs Unsuitable for use during fasting because of the inherent risk of Hypoglycemia, use with caution. Consider dose adjustment. Metformin Modify timing of doses: Two thirds of dose at Iftar One third at suhur. Metformin Modify timing of doses: Two thirds of dose at Iftar One third at suhur. E Hui et al, BMJ, 26 june 2010, Volume 340; Al-Arouj M. et al, Recommendations for management of diabetes during Ramadan. Diabetes Care. 2010;33:
Who should be tested? MODY misdiagnosed as type 2 diabetes and sometimes type 1 diabetes. Mutations can be inherited (commonly) or de novo (rarely). What genes should be tested? Most common causes of MODY are mutations in GCK, HNF1A and HNF4A. Is genetic testing good healthcare policy? Change from expensive therapy to cheaper therapy – saves money. If you have a GCK mutation, you DO NOT have type 2 diabetes and you do not need any drugs or a diabetes doctor! MonogenicDiabetes.org
Event rate Months RR=2.88 ( ) 24 RR=1.99 ( ) RR=1.71 ( ) RR=1.00 Diabetes/CVD (n=1,148) No Diabetes/CVD (n=3,503) Diabetes/No CVD (n=569) No Diabetes/No CVD (n=2,796) OASIS Study Mortality by Diabetes and CVD Status Malmberg K, et al. Circulation. 2000;102: OASIS=Organization to Assess Strategies for Ischemic Syndromes
Micro albuminuria - dipstick negative > 2.5 mg/mmol males > 3.5 mg/mmol females mg/day Macrolbuminuria – dipstick positive > 25 mg/mmol both males and females > 300mg/day – diabetic nephropathy (low serum albumin = nephrotic syndrome Can be proteinuria negative in type 2 +/- e GFR < 60ml/min
Diabetic Nephropathy: pathological classification Class 1 – EM proven GBM thickening Class 2a – Mild mesangial expansion Class 2b – Severe mesangial expansion Class 3 - Nodular sclerosis ( KW lesions) Class 4 - Advanced sclerosis ( > 50% glomeruli) Tervaert TC et al J Am Soc Nephrol 2010 online
A1A2A3 Normal to mildly increased Moderately increased Severely increased <30 mg/g <3 mg/mmol mg/g 3-30 mg/mmol >300 mg/g >30 mg/mmol CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health and CKD is classified based on cause, GFR category, and albuminuria category (CGA). KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3: Accessed February 26, 2013 G1Normal or high≥90 G2Mildly decreased60-89 G3a Mildly to moderately decreased G3b Moderately to severely decreased G4Severely decreased15-29 G5Kidney failure<15 GFR categories (ml/min/ 1.73 m²) Description and range Persistent albuminuria categories Description and range Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk. Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2012
A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99m Tc-diethylene-triamine- penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria. A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99m Tc-diethylene-triamine- penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria. Conclusion: patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric. MacIsaac et al, Diabetes Care Jan;27(1):
CHEP 2014 (BP target) ¹ Target Blood pressure Should be less than 140/90 mmHg in most patients, including those with chronic kidney disease. ESC 2013 (BP target) ² Target Blood pressure <140/90 mmHg should be considered in patients with diabetic or non-diabetic CKD. JNC IV (BP target) ³ In patients with CKD, initiate treatment at SBP ≥140 mmHg or DBP ≥90 mmHg, and treat to achieve SBP <140 mmHg and DBP <90 mmHg. 1: Canadian Hypertension Education Program (CHEP) 2014 Recommendation, adopted from: https://www.hypertension.ca/chep. Accessed at 5/2/2014 2: Mancia G, et al. J Hypertens Jul;31(7): : James PA, et al. JAMA Dec 18. [Epub ahead of print]
Intensive group n=80 Weight loss Exercise Smoking cessation BP & Lipid targets Aspirin, Statin, ACEI Compared to usual diabetic care 8 years follow up CV morbidity & mortality - 50% Progression to proteinuria - 60% Progression to Retinopathy - 60% Gaede P et al. Multifactorial intervention, N Engl J Med 2003; 348:
Steno-2 Trial: multiple risk factor intervention in T2DM Steno-2: Number needed to treat Number of microalbuminuric patients with type 2 diabetes needed to treat for 13 years to prevent one ….. Death 5 patients Cardiovascular death 8 patients Major cardiovascular event 3 patients Progression to nephropathy5 patients Dialysis16 patients Laser treatment7 patients
Aliskerin 300mg increased urinary albumin excretion Dual caused reduction of e GFR Stroke placebo 85 Aliskerin 112 Study discontinued
CKD 1-2CKD 3-4 Life style modification Protein intake 0.8g/kg Treat all risk factors HbA1C <7% BP < 140/80 Refer to Nephrologist : -rapid progressors - nephrotic syndrome - haematuria - e GFR < 40ml/min Same as CKD1-2 CKD group education: -Bone mineral disease - phosphorus mg/day - salt intake <6g/day - anaemia Hb 10-12g/dl - ferritin >100ng/ml Preparation for renal replacement therapy including transplantation
Microalbuminuria remains the gold standard Other candidate markers associated with microalbuminuria or low e GFR: - Neutrophil gelatinase associated lipocalin (NGAL) - Kidney Injury Molecule 1(KIM 1), -Transforming Growth Factor Beta -Cystitis C -Tumour Necrosis Factor -oocytes Adipocytokinine Zinc alpha 2 glyco protein (ZAG) in non-albuminurics
Glycaemic control Control oedema Debridement Dressings
Incidence and prevalence is high worldwide Effects up to 52% of men (40-70yrs) Aetiology - Organic - Hormonal - Anatomical - Drugs - Psychogenic
Diabetes continues to be a global epidemic particularly effecting the Middle East The ultimate goal of the congress is to support thaw commitment of health professionals to fight against diabetes. We hope you have gained more knowledge yet again this year and see you again at PACD in Cairo.