A standardised case record form was completed by the study team by questioning subjects and by reference to the ‘health passport’ carried routinely by patients in Malawi. Information was obtained about demographic details, date of diagnosis of diabetes, as well as anti-diabetic, anti-hypertensive, and anti-retroviral (ART) medications. Assessment of past medical history included presence or absence of stroke, ischaemic heart disease, neuropathy, foot ulcers, amputation, erectile dysfunction, previous diagnosis of tuberculosis, previous diagnosis of syphilis, diagnosis of malaria within the past year, and previous eye examination. Smoking was defined as current, former or never.
Box 5.2 Summary features of ‘ketosis prone atypical’ and ‘malnutritional-related’ diabetes [after reference 195]
Ketosis prone atypical Malnutrition-related
Ketotic presentation Insidious onset Children or young adults Young adults 3:1 male excess 2:1 Male excess
Islet autoimmunity rare Occasional ‘type 1’ HLA pattern Often strong family history Past or present malnutrition Remission possible Steatorrhoea in some areas
103 Physical examination was undertaken by a trained nurse or trained research
assistants who were part of the study team. Blood pressure was measured using the United Kingdom Prospective Diabetes Study (UKPDS) protocol [14] (HEM-907 XL, Omron, Lake Forest, IL). Subjects were classified as hypertensive according to the WHO definition [17]: subject either taking antihypertensive medication, or systolic blood pressure (sBP) ≥140mmHg, or diastolic blood pressure (dBP) ≥ 90mmHg. Weight (Seca 875, Birmingham, UK) and height were recorded. VA (uncorrected and using pinhole) was measured as the number of letters read on a standard Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (Sussex Vision, UK) using a standard protocol (testing at 4 metres initially and then at 1 metre if <20 letters are read at 4 metres). For illiterate subjects a 4m logarithm of the minimum angle of resolution (logMAR) ‘Tumbling E’ chart was used (Sussex Vision, UK). For each subject with VA in the better eye <80 letters I recorded what was, according to my clinical judgement, the primary cause of visual impairment. Causes of visual impairment were classified as DR, cataract, DR and cataract, age- related macular degeneration, glaucoma and ‘other’.
HIV status was defined as ‘unknown’, ‘known HIV positive not taking ART’, ‘known HIV positive taking ART’, or ‘known HIV negative’ (documented negative HIV test within 1 month). All subjects in the first 2 categories were offered HIV point of care testing according to Malawian national protocol [306] (Determine Rapid Test, Abbott, Hoofddorp, the Netherlands; Uni-Gold Recombigen, Trinity Biotech, Bray, Ireland; Bioline, SD, Korea). Those subjects diagnosed with HIV were referred to the dedicated HIV clinic at QECH from which ART is available. Haemoglobin was
measured with a point of care test (Hb301, HemoCue, Angelholm, Sweden). Thresholds for anaemia were set according to WHO guidelines: 13.0g/dL for men; 12.0g/dL for women [307].
Blood samples were assayed for putative biochemical risk factors: fasting glucose, triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, serum creatinine, and urine albumin-creatinine ratio (ACR)
104 (colorimetric assays performed at Malawi Liverpool Wellcome laboratories,
Blantyre, Malawi using the Synchron CX5, Beckman Coulter, CA). Glycosylated haemoglobin (HbA1c) was measured using Boronate affinity chromatography performed at Norfolk and Norwich University Hospitals Laboratories, UK. A detailed description of HbA1c measurement in the MDRS is given below in Section 5.12. Hypercholesterolaemia was defined according to the WHO as ≥ 5.0 mmol/L [17]. Photographs of the MDRS study team assessing subjects are shown in Figure 5.1.
105 Figure 5.1 Photographs of the MDRS study team assessing study subjects.
Photograph A: Sister Chrissy Pindani taking a venous blood sample. Photograph B: Research Assistant Moffat Chidzuwa measuring visual acuity using a 4m logMAR ‘Tumbling E’ chart.
106
5.9.4 Assessment of retinopathy
Digital fundus photography of four 45° standard fields [94] with a stereo macular image was performed through dilated pupils (guttae tropicamide 1% and
phenylephrine 2.5%) using CR6 fundus cameras (Canon, Reigate, UK). Photographic fields used in the MDRS are shown in Figure 5.2. MDRS standards for field position and quality are shown in Figure 5.3. Dual grading of photographic images was performed by accredited graders at the Liverpool Ophthalmic Reading Centre (an accepted reference standard for grading of retinopathy). In the event of
disagreement between graders arbitration was performed by a senior
ophthalmologist accredited in grading. Graders followed protocols established in Liverpool. Briefly, images were graded on graphic quality monitors against photographic standards defined for the ETDRS on standardised data forms in sessions lasting a maximum of 2 hours before a break, to ensure adequate quality.
In addition to fundus photographs, all subjects were examined by me (PB) using slit-lamp biomicroscopy. Cataract was graded according to the Lens Opacities Classification System (LOCS) III [308] and considered clinically significant when graded at ≥3 in any category (nuclear opalescence, nuclear colour, cortical or posterior subcapsular). A photograph of the MDRS study team performing retinal photography is shown in Figure 5.4.
107 Figure 5.2. Photographic fields used in the MDRS. Digital fundus photography of four 45° standard fields with a stereoscopic macula image were performed. Illustrations show the right eye. Circle indicates the optic disc; cross indicates the centre of the fovea. Field 1: Disc centred image. Field 2. Macular centred stereo image (2 images: a and b). Field 3: Superior temporal image. Positioned with the disc in the 5 o'clock or 7 o'clock positions for upper temporal quadrant in the right and left eyes, respectively. All of the disc should be visible with the disc margin abutting the edge of the image. Field 4: Inferior temporal image. Disc in the 1 o'clock or 11 o'clock positions for the lower temporal quadrant in right and left eyes, respectively.
108 Figure 5.3. Standards for photograph field position and image quality used in the MDRS