Diabetes and Its Long-Term Complications.

A Clinical Case Report
Author: Nuha Emad Awada
Medical school: Jordan University of Science and Technology (JUST)

Introduction

Diabetes mellitus is a common chronic metabolic disorder characterized by persistent hyperglycemia resulting from inadequate insulin secretion, impaired insulin action, or both. Long-standing hyperglycemia can damage multiple organ systems and lead to microvascular and macrovascular complications.

According to the Centers for Disease Control and Prevention (CDC), an estimated 40.1 million people in the United States had diagnosed or undiagnosed diabetes in 2023. Diabetes is associated with an increased risk of cardiovascular disease, kidney disease, neuropathy, retinopathy, foot ulceration, and lower-extremity amputation.

This case illustrates the potential consequences of prolonged untreated or poorly monitored type 2 diabetes in a patient who had gone approximately five years without routine medical follow-up or recommended screening.

How Chronic Hyperglycemia Causes Complications

Chronic hyperglycemia produces cellular and vascular injury through several interrelated biochemical pathways. Excess intracellular glucose increases activity of the polyol pathway, contributing to sorbitol accumulation, NADPH depletion, oxidative stress, and cellular injury. Hyperglycemia also increases diacylglycerol (DAG) and protein kinase C (PKC) activity, contributing to endothelial dysfunction, altered vascular permeability, and inflammation. Increased flux through the hexosamine pathway can alter protein and gene regulation and contribute to abnormal extracellular matrix deposition. Together, these mechanisms contribute to progressive neurological, vascular, retinal, and renal injury.

Clinical Case Presentation

A 57-year-old Hispanic man with a more than 20-year history of type 2 diabetes mellitus presented to a clinic for a disability evaluation. He reported that he had not attended routine medical follow-up or undergone recommended screening for approximately five years. He attributed his lack of medical care primarily to financial and insurance-related difficulties and hoped that obtaining disability status would provide access to medications, screening, and other medical services.

At presentation, he reported excessive thirst, increased hunger, polyuria, severe fatigue, and blurred vision. He also described longstanding tingling, numbness, and swelling involving both the upper and lower extremities. These sensory symptoms had not previously been formally evaluated or treated.

The patient reported that his last ophthalmologic evaluation had been approximately five years earlier. He also reported a family history of diabetic retinopathy and currently experienced blurred vision.

His diabetic history was complicated by significant lower-extremity disease. In 2024, he developed an ulcer of the great toe that became severely infected and ultimately required amputation of the affected great toe. Subsequently, he developed another ulcer on the plantar surface of the foot. At the time of presentation, he reported that the ulcer was extremely painful and appeared infected. The condition had impaired his mobility, and he walked with a limp.

The patient reported diabetes mellitus in both his maternal and paternal family histories. He acknowledged awareness of the potential complications of diabetes but had continued to defer medical evaluation and treatment.

He described his diet as generally balanced, consisting primarily of protein, vegetables, and fruit, with occasional fast-food consumption. He reported occasional alcohol use, typically one beer. He was a former smoker and reported that he had stopped smoking approximately 17 years earlier. He also reported daily physical activity, including push-ups, sit-ups, and jumping jacks.

The patient worked as a chef at BJ’s and reported prolonged periods of standing. He stated that his feet frequently became wet during work, particularly during cleaning activities at the end of his shift, and that he did not always dry his feet thoroughly afterward. This occupational exposure is clinically relevant in the setting of an active chronic foot ulcer.

He denied known hypertension, hyperlipidemia, sleep apnea, and paroxysmal nocturnal dyspnea. However, his blood pressure was markedly elevated at 184/99 mmHg on presentation and remained elevated at 168/100 mmHg approximately 30 minutes later, raising concern for previously unrecognized or untreated hypertension.

He also reported approximately one year of acid reflux. He stated that his last electrocardiogram had been approximately 20 years earlier and that he had not undergone recent cardiovascular evaluation. His only reported prior surgery was the great-toe amputation in 2024.

Major Diabetes-Related Complications Illustrated by the Case

Peripheral Neuropathy

The patient’s longstanding tingling and numbness of the extremities are concerning for diabetic peripheral neuropathy. Loss of protective sensation can allow minor injuries to go unnoticed and can increase the risk of foot ulceration and infection. Current American Diabetes Association (ADA) guidance recommends assessment for diabetic peripheral neuropathy beginning at the diagnosis of type 2 diabetes and at least annually thereafter.

Diabetic Foot Ulceration and Prior Amputation

The history of a severely infected great-toe ulcer requiring amputation, followed by another plantar foot ulcer, places this patient in a high-risk category for recurrent ulceration and further limb complications. Neuropathy, peripheral arterial disease, foot deformity, prior ulceration, prior amputation, smoking history, and kidney disease can all contribute to diabetic foot risk. The presence of an open ulcer or suspected infection warrants prompt clinical assessment.

Possible Diabetic Retinopathy

Blurred vision after approximately five years without ophthalmologic screening raises concern for diabetic retinopathy or another ocular disorder. Importantly, the case does not establish a diagnosis of diabetic retinopathy because no recent ophthalmologic examination or retinal findings are provided. For people with type 2 diabetes, the ADA recommends a comprehensive dilated eye examination at the time of diagnosis, with subsequent screening intervals determined by retinal findings and individual risk.

Cardiovascular and Vascular Risk

Diabetes substantially increases cardiovascular risk and is associated with peripheral arterial disease and other vascular complications. The patient’s markedly elevated blood pressure on two measurements also raises concern for previously unrecognized or untreated hypertension. The available case information does not establish coronary artery disease or peripheral arterial disease, so these should be considered clinical concerns requiring evaluation rather than confirmed diagnoses.

Possible Kidney Involvement

The case discusses the renal consequences of diabetes in general, but it does not provide laboratory data establishing chronic kidney disease in this patient. Assessment of kidney function and urine albumin excretion would be appropriate when evaluating a person with long-standing type 2 diabetes, particularly when other end-organ complications are present.

Discussion

This case demonstrates how prolonged gaps in diabetes care can allow multiple complications to develop without timely detection or intervention. The patient’s neuropathic symptoms, history of an infected foot ulcer requiring amputation, recurrent plantar ulceration, and visual symptoms are clinically significant. His markedly elevated blood pressure adds another potentially modifiable cardiovascular risk factor.

The case also highlights the importance of access to care. Although the patient reported that he had deferred care partly because of financial and insurance-related difficulties, the clinical consequences illustrate the potential cost of delayed screening and treatment. Early identification and management of hyperglycemia, hypertension, lipid abnormalities, neuropathy, retinopathy, kidney disease, and foot complications can reduce the risk of severe morbidity.

Prevention and Routine Monitoring

  • Regular monitoring of glycemic control and individualized glucose-lowering therapy.
  • Blood-pressure assessment and treatment when hypertension is confirmed.
  • Regular assessment for diabetic kidney disease, including appropriate laboratory testing.
  • Routine comprehensive eye examinations and prompt ophthalmologic evaluation when visual symptoms occur.
  • At least annual assessment for diabetic peripheral neuropathy and loss of protective sensation, with more frequent evaluation in high-risk patients.
  • At least annual comprehensive foot evaluation, with inspection at every visit for patients with prior ulceration or amputation.
  • Prompt evaluation of any new foot ulcer, redness, swelling, drainage, pain, or suspected infection.
  • Lifestyle measures including a balanced diet, physical activity appropriate to the patient’s medical condition, smoking cessation, and maintenance of a healthy body weight.

Conclusion

Long-standing type 2 diabetes can affect the nervous system, eyes, kidneys, cardiovascular system, and lower extremities. This case illustrates the consequences that may occur when routine follow-up and recommended screening are interrupted for several years. The patient’s sensory symptoms, recurrent foot ulceration and prior amputation, visual complaints, and markedly elevated blood pressure demonstrate the importance of comprehensive diabetes care and early recognition of complications.

Important Clinical Note

This article is intended for educational and informational purposes. It is not a substitute for individualized medical evaluation, diagnosis, or treatment. A patient with an active or suspected infected diabetic foot ulcer, new visual changes, markedly elevated blood pressure, or other concerning symptoms should receive timely professional medical assessment.

References

  1. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Updated 2026. https://www.cdc.gov/diabetes/php/data-research/index.html
  2. American Diabetes Association Professional Practice Committee for Diabetes. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1):S261–S276. https://doi.org/10.2337/dc26-S012
  3. American Diabetes Association Professional Practice Committee for Diabetes. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1):S216–S260. https://doi.org/10.2337/dc26-S010
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How Low is Low?

RISKS OF VERY LOW LDL CHOLESEROL LEVEL

By Laura Edith Chavez Salas
Universidad De Durango, Campus Zacatecas, Mexico

Amin H. Karim, MD
Houston Methodist Academic Institute

Low-density lipoprotein (LDL) represents a category of lipoprotein particles responsible for the transport of cholesterol and various lipids within the bloodstream. Often referred to as the “bad” cholesterol, it serves vital purposes. LDL particles serve as the primary carriers of cholesterol to peripheral tissues and consist of cholesteryl esters and triglycerides encased in a phospholipid shell, free cholesterol, and a single molecule of apolipoprotein B-100. Increased levels of LDL are directly associated with the onset of atherosclerotic cardiovascular disease (ASCVD), as LDL particles can penetrate the arterial wall, become retained and altered (for instance, oxidized), and facilitate the development of foam cells and atherosclerotic plaques. (1-4)

LDL exhibits heterogeneity, with subclasses that vary in size and density; smaller, denser LDL particles are deemed more atherogenic compared to their larger, more buoyant counterparts. (3, 5, 6) The cholesterol content within LDL particles is quantified as LDL cholesterol (LDL-C), which serves as a conventional marker for evaluating and managing cardiovascular risk. (7) Nevertheless, the quantity of LDL particles (LDL-P) and the concentration of apolipoprotein B (apoB) may offer further risk stratification, particularly in individuals with metabolic syndrome or diabetes, as discrepancies between LDL-C and LDL-P can arise. (8) Evaluation of ASCVD risk can be evaluated by assessing both LDL-C and LDL-P, asserting that the reduction of LDL—primarily through the use of statins and other lipid-lowering treatments—leads to a decrease in cardiovascular events. (4)

DANGERS OF VERY LOW LDL

However, an LDL-lowering regimen can lead to ultra-low-density lipoprotein cholesterol (LDL-C) levels. These are typically defined as <40–50 mg/dL, and especially <30 mg/dL. These levels are generally well tolerated and associated with a reduced risk of atherosclerotic cardiovascular disease (ASCVD), but several potential dangers have been identified. (9) Mechanistically, very low LDL-C may impair endothelial integrity and platelet function. This could potentially increase bleeding risk, especially for intracranial and gastrointestinal hemorrhage. (10, 11)

The most observed danger of ultra-low LDL is a possible hemorrhagic stroke and other bleeding events, particularly at LDL-C levels below 40 mg/dL, as supported by mechanistic and clinical data. Observational studies and meta-analyses have also reported a U-shaped relationship between LDL-C and all-cause mortality, with both very low (<50 mg/dL) and high (≥130 mg/dL) LDL-C levels associated with increased mortality in certain populations, such as those with coronary artery disease. (15)

There is also some evidence suggesting a potential association between ultra-low LDL-C and increased risk of new-onset diabetes mellitus, particularly with statin therapy. Leading to more complications, there is a possible link to cataract formation and glaucoma, though causality remains unproven and the absolute risk is low. (11, 14)

The main dangers of ultra-low LDL-C are a possible increased risk of hemorrhagic stroke, new-onset diabetes, and, less consistently, all-cause mortality in specific populations. However, for most high-risk patients, the cardiovascular benefits of aggressive LDL-C lowering outweigh these potential risks. (9-14)

HIGH-RISK PATIENTS

Patients at highest risk for complications associated with very low levels of low-density lipoprotein cholesterol (LDL-C) are:

• Individuals with a prior history of hemorrhagic stroke:

The American Stroke Association notes that the risk of hemorrhagic stroke with statin therapy is small and nonsignificant in those without prior cerebrovascular disease, but patients with a history of hemorrhagic stroke may be at increased risk, and lipid lowering in this group requires individualized consideration and further study. (16)

• Patients with poorly controlled hypertension and very low LDL-C:

There is literature that indicates that the combination of very low LDL-C (especially ≤40 mg/dL) and uncontrolled hypertension substantially increases the risk of both ischemic and hemorrhagic stroke. Although this risk is particularly more prevalent in East Asian populations, it is relevant globally. (17)

• Women with LDL-C <70 mg/dL:

There is evidence from long-term cohort studies in women that has shown that LDL-C <70 mg/dL is associated with a more than twofold increased risk of hemorrhagic stroke compared to LDL-C 100–129.9 mg/dL, independent of other risk factors. Meaning that women with no other risk factors have more risk than males with no other risk factors. (18)

• Patients on intensive statin therapy or with other risk factors for diabetes: Statin therapy, especially at high intensity, is associated with a modestly increased risk of new-onset diabetes. Particularly in those with predisposing factors such as metabolic syndrome or impaired fasting glucose. (11)

Risks associated with having ultra-low LDL-C are more prevalent in populations most at risk, which are those with prior hemorrhagic stroke, poorly controlled hypertension, women, and individuals with multiple vascular risk factors or on intensive lipid-lowering therapy. 

REFERENCES

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  3. Qiao, Ya-Nan et al. “Low-density lipoprotein particles in atherosclerosis.” Frontiers in physiology vol. 13 931931. 30 Aug. 2022, doi:10.3389/fphys.2022.931931
  4. Maurya, Rupesh et al. “Low density lipoprotein receptor endocytosis in cardiovascular disease and the factors affecting LDL levels.” Progress in molecular biology and translational science vol. 194 (2023): 333-345. doi:10.1016/bs.pmbts.2022.09.010
  5. Ivanova, Ekaterina A et al. “Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases.” Oxidative medicine and cellular longevity vol. 2017 (2017): 1273042. doi:10.1155/2017/1273042
  6. Packard, C et al. “The role of small, dense low density lipoprotein (LDL): a new look.” International journal of cardiology vol. 74 Suppl 1 (2000): S17-22. doi:10.1016/s0167-5273(99)00107-2
  7. Jialal, I, and A T Remaley. “Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.” Clinical pharmacology and therapeutics vol. 96,1 (2014): 20-2. doi:10.1038/clpt.2014.69
  8. Galimberti, Federica et al. “Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment.” Pharmacological research vol. 195 (2023): 106873. doi:10.1016/j.phrs.2023.106873
  9. Karagiannis, Angelos D et al. “How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol.” European heart journal vol. 42,22 (2021): 2154-2169. doi:10.1093/eurheartj/ehaa1080
  10. Siniscalchi, Carmine et al. “Low LDL-Cholesterol and Hemorrhagic Risk: Mechanistic Insights and Clinical Perspectives.” International journal of molecular sciences vol. 26,12 5612. 11 Jun. 2025, doi:10.3390/ijms26125612
  11. Cure, Erkan, and Medine Cumhur Cure. “Emerging risks of lipid-lowering therapy and low LDL levels: implications for eye, brain, and new-onset diabetes.” Lipids in health and disease vol. 24,1 185. 21 May. 2025, doi:10.1186/s12944-025-02606-6
  12. Olsson, A G et al. “Can LDL cholesterol be too low? Possible risks of extremely low levels.” Journal of internal medicine vol. 281,6 (2017): 534-553. doi:10.1111/joim.12614
  13. Rong, Shuang et al. “Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population.” Journal of the American Heart Association vol. 11,15 (2022): e023690. doi:10.1161/JAHA.121.023690
  14. Faselis, Charles et al. “Is very low LDL-C harmful?.” Current pharmaceutical design vol. 24,31 (2018): 3658-3664. doi:10.2174/1381612824666181008110643
  15. Scudeler, Thiago Luis et al. “Association between low-density lipoprotein cholesterol levels and all-cause mortality in patients with coronary artery disease: a real-world analysis using data from an international network.” Scientific reports vol. 14,1 29201. 25 Nov. 2024, doi:10.1038/s41598-024-80578-w
  16. Goldstein, Larry B., et al. “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.” Arteriosclerosis Thrombosis and Vascular Biology, vol. 43, no. 10, Sept. 2023, https://doi.org/10.1161/atv.0000000000000164.
  17. Wu, Zhijun et al. “The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations < 70 mg/dL.” BMC medicine vol. 19,1 142. 16 Jun. 2021, doi:10.1186/s12916-021-02014-4
  18. Rist, Pamela M et al. “Lipid levels and the risk of hemorrhagic stroke among women.” Neurology vol. 92,19 (2019): e2286-e2294. doi:10.1212/WNL.0000000000007454

Jailed Semi-Inflated Kissing Balloon Technique

By Dr. Naeem Tahirkheli
Oklahoma, USA


Talking JSKBT ( jailed semi inflated kissing balloon technique ) We did multiple JSKBTs here. Zameer our Pakistani fellow made these images.

Patient had CP/ NSTEMI in a decent sized town 100 miles away. Which has good sized hospital and interventional cardiologist’s and PCIs / primary etc are done. No CABG onsite. Cardiologist did angio for intervention purposes. Saw the anatomy
Calcified distal left main, Ostial/ prox / mid LAD, 90% tight ramus, 90% bifurcation LCX/OM1 and CTO RCA. EF 30% with severe MR ( so even poorer forward flow / and overestimation of the LV function due to MR).

Referred to our surgeon. He said he can ! But very high risk. ( calcified aorta not. Great candidate to put on heart lung bypass / previous EVAR, Poor LV function, ) so referred to one of our colleagues – who said very high risk PCI. Referred back to surgery. Nothing happened. Meanwhile patient having symptoms. So the primary interventional cardiologist from the other city called us.
Was going to need 3 to 4 wires with multiple balloons at a time. So needed an 8 French guide so did do single access Impella. Also deliberately took a short JL 3.5 guide ( which obviously has low support ) so we can sit outside this shortish left main and work

LAD was quite retroflex so you can appreciate flipping of hydrophilic coated wire with >120 bend with microcatheter assistance. Later changed to wiggle wire; So onwards LAD was started. Calcified, retroflex and quite some tortuous so IVUS was done after first run of 2.5 pre-dil;
Still there was IVUS malfunction in mid autorun so predilated with 3.0 balloon and ReIVUS
Heavy more than 270 degrees calcium is there;
Further vessel preparation was done with 3.0 IVL all the way upto LMS

This is tight LCX and tight OM1. Kissing balloon inflations and then stent in LCX and JSKBT is OM. Notice 4 wires in there. Pretty good result. OM Latium looks really good. IVUD of LCX stent good. Did POT of the proximal LCX with NC balloon; This is the long 3.0 x 48 synergy xl. Extending from mid LAD to left main and have 3.0 x 15 balloons as JSKBTs in Intermediate and LCX

Couldn’t get the IVUS to distal edge to see if it is dissection or spasm. These new Hi Def boston IVUS shafts are flimsy and you push them and they get bent. Used three different catheters during this long intervention. Cuz it would get stuck in calcium and then either stop working or the shaft get bent. So images look like distal edge dissection. Placed a 2.5 mm shirt stent. Looked good after wards

IVUS from LAD stent back to left main. Had also done a 4.5 x 6 mm short NC balloon POT for left main. ( size mismatch between left main and LAD)

Of course without Impella. Wouldn’t have been able to do these. With occluded RCA and EF 30% with severe MR. I was getting flat line pressures with IVL and Thenleft main stenting with JSKBTs


The End